Front. Chem. Frontiers in Chemistry Front. Chem. 2296-2646 Frontiers Media S.A. 1078840 10.3389/fchem.2023.1078840 Chemistry Review Hierarchy of hybrid materials. Part-II: The place of organics-on-inorganics in it, their composition and applications Song et al. 10.3389/fchem.2023.1078840 Song Junnan 1 * Vikulina Anna S. 2 Parakhonskiy Bogdan V. 1 * Skirtach Andre G. 1 * 1 Nano-BioTechnology Group, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium 2 Bavarian Polymer Institute, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bayreuth, Germany

Edited by: Claudia Caltagirone, University of Cagliari, Italy

Reviewed by: Rajendra Kurapati, Indian Institute of Science Education and Research, Thiruvananthapuram, India

Dario Pasini, University of Pavia, Italy

 *Correspondence: Junnan Song, Junnan.Song@UGent.be; Bogdan V. Parakhonskiy, bogdan.parakhonskiy@ugent.be; Andre G. Skirtach, andre.skirtach@ugent.be

This article was submitted to Supramolecular Chemistry, a section of the journal Frontiers in Chemistry

 25 01 2023 2023 11 1078840 24 10 2022 05 01 2023 Copyright © 2023 Song, Vikulina, Parakhonskiy and Skirtach. 2023 Song, Vikulina, Parakhonskiy and Skirtach

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Hybrid materials or hybrids incorporating organic and inorganic constituents are emerging as a very potent and promising class of materials due to the diverse but complementary nature of their properties. This complementarity leads to a perfect synergy of properties of the desired materials and products as well as to an extensive range of their application areas. Recently, we have overviewed and classified hybrid materials describing inorganics-in-organics in Part-I (Saveleva, et al., Front. Chem., 2019, 7, 179). Here, we extend that work in Part-II describing organics–on-inorganics, i.e., inorganic materials modified by organic moieties, their structure and functionalities. Inorganic constituents comprise of colloids/nanoparticles and flat surfaces/matrices comprise of metallic (noble metal, metal oxide, metal-organic framework, magnetic nanoparticles, alloy) and non-metallic (minerals, clays, carbons, and ceramics) materials; while organic additives can include molecules (polymers, fluorescence dyes, surfactants), biomolecules (proteins, carbohydtrates, antibodies and nucleic acids) and even higher-level organisms such as cells, bacteria, and microorganisms. Similarly to what was described in Part-I, we look at similar and dissimilar properties of organic-inorganic materials summarizing those bringing complementarity and composition. A broad range of applications of these hybrid materials is also presented whose development is spurred by engaging different scientific research communities.

 hybrid materials organics inorganics nanoparticles colloids flat surfaces modifications and applications 1 Introduction

The growth of research in the area of hybrid materials is continuing to be robust, benefiting from advanced processing methods (Lutich et al., 2009; Yang et al., 2019; Ariga et al., 2020), emerging technologies (Moreels et al., 2008; Zhu et al., 2021) and materials (Gaponik and Rogach, 2010; Yan et al., 2014; Zuaznabar-Gardona and Fragoso, 2018; Karthick et al., 2022), which facilitate tremendous growth and establish interconnections between associated scientific research areas and create new functionalities (Balazs et al., 2006; Christau et al., 2014; Leroux et al., 2015; Cui et al., 2016; Gao et al., 2016; Taubert et al., 2019; Cao et al., 2022; Stavitskaya et al., 2022). In the past, different approaches to the classification of hybrid materials have been discussed: those based on the interactions (Sanchez and Soler-Illia, 2006), wherein those associated with van der Waals, hydrogen bonding, and electrostatics are distinguished from those based on covalent and no-covalent bonds. On the other hand, distinction was made based on their composition (Kickelbick, 2003; Saveleva et al., 2019).

Recently and in the latter work, classification of “hybrid materials” was performed by Saveleva and co-authors, where modification of organic materials by inorganics was analyzed (Saveleva et al., 2019). It was emphasized that perfect complementarity of these two types of materials stemming from the fact that they are used to improve their respective properties or to bring-in additional functionalities into resultant hybrid materials (Ruiz-Hitzky et al., 2008; Wang et al., 2018b; Guo et al., 2020; Li et al., 2021a). A typically highlighted example is an assembly of hard and soft–two antagonist properties–materials which are different but complementary in regard with their properties. Peculiarly, such modifications have been used even from the time of ancient Greece (Sanchez et al., 2005) to particle-enhanced tires fabricated using carbon black, ZnO, MgS with rubber (Goodyear, 1856), extending to one a very practical material Bakelite produced by Leo Baekeland by admixing clays with resin (Baekeland, 1909). In contemporary research and development areas, functionalities and applications of hybrid materials continue to be extended, including, for example, water purification (Rigoletto et al., 2022) and antibacterial properties (Chen et al., 2022).

Hybrids were structurally and compositionally classified as follows (Saveleva et al., 2019):

i) Inorganic-modified organic materials (inorganics-in-organics);

ii) Organic molecule-modified inorganic materials (organics-on-inorganics), which can be sub-divided into:

a) Colloids and nanoparticles functionalized by organic molecules;

b) Inorganic structures modified and functionalized by organic molecules.

This review discusses the modification of inorganic materials and matrices by organic molecules, organics-on-inorganics (ii). The structure of these hybrid materials is discussed together with interactions of constituent blocks and applications. It thus provides the second part of the previously described Part-I by (Saveleva et al., 2019), which discussed inorganics-in-organics.

The hierarchy or classification of organics-on-inorganics is presented in Figure 1 and is extended analysing their composition, structure, chemical bonds, properties and functionalities, and applications. There, Part-I (Saveleva et al., 2019) is seen in grey rectangles (right-hand side), which introduced some modifications and functions of inorganics covering a range of materials from inorganic minerals, clays, metals, semiconductors, carbons, ceramics to organic ones: hydrogels, layer-by-layer (LbL) assembled polymer structures, brushes, and so on. Here, we focus on modifying inorganic particles, structures, and matrices with organic molecules–highlighted part (on the left-hand side) in Figure 1—and discuss their composition, interactions, and applications. Then, organic molecules and modifiers (organics) are introduced identifying the range of properties they can enable. Subsequently, we generally describe hybrid materials, summarize their properties, and provide conclusions and outlook.

General classification of hybrid materials incorporating both organic and inorganic components. Adsorption of organic molecules on inorganic particles, structures, or matrices, referred to as organics-in-inorganics, is shown on the right-hand side in the grey-dashed rectangle constituted the Part-I of this classification (Saveleva et al., 2019). Functionalization of both inorganic colloidal particles and flat surfaces by organic molecules referred to as organics-on-inorganics, shown on the left-hand side, is the focus of this review. The bottom rows depict composition, chemical bonds, properties, and functionalities leading to development of a broad range of applications.

 2 Inorganic colloidal particle functionalization by organic molecules

Developments in the area of colloidal particles has had a particularly profound impact in the field of biomedical applications including bioactive molecule sensing, targeted drug delivery, release systems, selective imaging agents, and diagnostics (Parakhonskiy et al., 2014; Tarakanchikova et al., 2020; Zhou et al., 2021). One of the reasons nanoparticles (NPs) are appealing for applications in biomedicine is because nano-size objects possess unique physicochemical properties, especially in a combination with an external electromagnetic field, which can mediate biological responses, for example, enhancing 1O2 generation (Sun et al., 2020a). Arguably, one of the most notable advantages brought by the NPs is the enhanced permeability and retention (EPR), which is considered to be a “golden standard” for designing new anticancer agents. Due to the EPR passive targeting and active endocytosis, cellular uptake (Figure 2) of nanocarriers could significantly improve anticancer/tumour drug efficiency and reduce their side effect and even rediscover drugs that may have tested failed clinically applications (Duan et al., 2019; McMahon et al., 2020; Peer et al., 2020; Majumder and Minko, 2021).

Schematic diagram of active and passive absorption of nanomedicines (Majumder and Minko, 2021), with the permission of the Wiley Online Library.

Compared with organic NPs, inorganic NPs’ inherent unique conductivity, magnetism, optical properties and variety in size, structure, and shape have become the hot spot in therapeutic diagnosis (Tan et al., 2018; Wang et al., 2018a; Sun et al., 2020b), whereas one of the broadest areas of research applying organic NPs is drug delivery. For example, superparamagnetic NPs can enhance magnetic resonance imaging (MRI) contrast, Au NPs are widely used in catalysis, drug delivery, imaging and photothermal therapy (Wang et al., 2006; Cui et al., 2014; Xiong et al., 2014; Fraire et al., 2019), while carbon quantum dots (CQDs) have inspired development of numerous applications particularly in biosensing and bioimaging due to their optical and fluorescence emission properties (Lim et al., 2015). Further, Figure 3 summarizes inorganic colloidal structures often functionalized with denoted organic molecules. Figure 4 summarizes applications of inorganic colloids modified by organics, particularly relevant in biomedical applications, and Table 1 summarizes selected applications of hybrid colloidal particles, where biomedicine is identified to be one of the most widely used application areas.

Organic molecules often used for inorganic NP functionalization in biomedical applications. The inorganic constituents (inside orange frame): noble metals (TEM images of Au NPs and Ag NPs reproduced from (Parakhonskiy et al., 2010), with permission from the RSC); metal oxides (TEM image of TiO2 NPS reproduced from (Sang et al., 2014) with permission from ACS); metal organic framework (MOFs; TEM image of Pt@MIL-101 reproduced from (Aijaz et al., 2012) with permission from ACS); magnetic NPs (TEM image of Fe3O4 reproduced from (Kozlova et al., 2020), with permission from MDPI); clays (TEM image of halloysite nanotubes reproduced from (Lvov et al., 2008), with permission from ACS), minerals (SEM image of CaCO3 microparticles reproduced from (Abalymo v et al., 2022), with permission from Elsivier, TEM image of SiO2 reproduced from (Ung et al., 2001), with permission from J. Phys.Chem.B), diamonds (TEM image of nanodiamonds reproduced from (Smith et al., 2009) with permission from Wiley-VCH. Organic molecules used for functionalization of inorganic particles and nanostructures are shown outside of the orange frame.

Functionalities provided by organic molecules adsorbed on inorganic NPs.

The overview of the studies of hybrid organics-on-inorganics colloidal and their composition, feature/functionalities.

Composition of hybrid colloids Functionalities and applications
Inorganic NPs Organic molecules and reference
Noble Metal Au 4-(dimethylamino)pyridine (DMAP) REF Fraire et al (2019), polydimethylsiloxane (PDMS) Zhu et al. (2021), catalytic hairpin assembly Song et al. (2021), nucleic acid hybridization, aptamer-target binding, antigen-antibody recognition, enzyme Hua et al. (2021) Selective and sensitive identification
Layer-by-layer, PEI Lee et al. (2011), high-density lipoprotein Shen et al. (2018) CpG oligodeoxynuleotides Duan et al. (2019) Hyaluronic acid (Ha) (Sanfilippo et al. (2020) PEG, poly-l-lysine (PLL) Oladimeji et al. (2021) Targeted delivery
l-lysine Volodkin et al. (2009) Remote release
Gallic acid Kim et al. (2017), hyaluronic acid Sanfilippo et al. (2020) Reduction of cytotoxicity
Au, Ag Conventional surfactants and ligands (PVP, CTAB, Citrate), polyol (EG, PEG) Zhang et al. (2011); Kang et al. (2019), thiol (-SH), amine (−NH2),carboxyl (−COOH), phosphine (−PR3), PEI Heuer-Jungemann et al. (2019); Kang et al. (2019); Roberts et al. (2020); Song et al. (2021) Morphology guide
Polymer (PEG) (Kang et al. (2019), Citrate Patungwasa and Hodak (2008); Wen et al. (2020) Cetyltrimethylammonium bromide (CTAB) Heuer-Jungemann et al. (2019) Stabilization preservation and improvement of plasmonic particle functionalities
DNA, protein Kang et al. (2019), Ferritin Moglia et al. (2021), pMPC King and Fiegel (2022) Enhancement of biocompatibility, programmable assembly
Ag Chitosan (CTS), Polyvinylpyrrolidone (PVP) (Zhang et al. (2012a) Pomegranate rind extract Panáček et al. (2018), Starch nanofiber mats Lv et al. (2021), Mentha pulegium extract Wang and Wei (2022) Stabilization
Melamine (1,3,5-triazine-2,4,6-triamine) Li et al. (2019) Label-free detection for targeted DNA delivery
Bisphosphonate alendronate Benyettou et al. (2015), folic acid Yang et al. (2021a) Targeted delivery
Citrate, PVP Gitipour et al. (2016) Starch nanofiber mats Lv et al. (2021) Reduction of cytotoxicity
MXene (Ti3C2Tx)-Ag Citrate, PDDA Liu et al. (2021) Efficient and quantitative SERS biosensor platform
Metal Oxide Bi2O2CO3-Cu2O Silk fibroin Ji et al. (2020a) Recyclable photocatalysts with enhanced photocatalytic activity, reduction of cytotoxicity
ZnO Reactive cyclic oligosaccharide: monochlorotriazinyl-β-cyclodextrin (MCT-β-CD), PEA Abdolmaleki et al. (2014) Stabilization (good dispersion and less aggregation)
Octylamine trioctylphosphine oxide, hexadecylamine, dodecylamine Heuer-Jungemann et al. (2019) Surfactant morphology guide
Polymer Zhao et al. (2017) pH-triggered drug-delivery system
TiO2 3-aminopropyltriethoxysilane (APTES), glutaraldehyde (GLU), laccase Hou et al. (2014) Increasing catalytic activity, thermal and operational stability
CuO Protease and amylase Murugappan and Sreeram (2021)
MnO2 Macrophage Li et al. (2021b) Good adsorption to target cells
Al2O3, SiO2 Polyurethane (PU) Xavier (2021) Enhancing anticorrosion
Metal-Organic Framework MIL-101(Fe)-NH2 Long-chain polyamines (ethylenediamine, 1,2-bis(3-aminopropylamino)ethane Almáši et al. (2018) Improving antibacterial, and biocompatible property
Zr MOF UiO-66 α-cyano-4-hydroxycinnamic acid (α-CHC), Alendronate Abanades Lazaro et al. (2020)
MIL101 NPs Zwitterionic hydrogel layer Zhou et al. (2021)
Cu-based MOFs Pectin nanofibers polyethene oxide (PEO), folic acid Kiadeh et al. (2021)
NiCo2O4, Au Nafion/thionine Li et al. (2011)
Magnetic nanoparticles Fe3O4, SiO2 Poly (ethylene glycol) (PEG), antibody Liu et al. (2020b) Target delivery
Fe3O4, SiO2 Poly (allylamine hydrochloride) (PAH) Shi et al. (2011) Enhanced biocompatible, reduction of cytotoxicity
Fe3O4 Polyethylene glycol, polypyrrole Song et al. (2014) Stabilization, target cell tumour uptake
Ultra-small superparamagnetic Fe3O4 Polydopamine, GE11 peptide Yang et al. (2019) Encapsulation drug carriers
Fe3O4, ZrO2 Glucose oxidase Haskell et al. (2020) Controlling catalytic performance and stability
Fe3O4 Hyaluronic acid Sun et al. (2021b) Good adsorption to multiple types of immune cells
Fe@Au Janus nanoparticles Polyvinylpyrrolidone (PVP) Espinosa et al. (2020) Magnetically guided and thermally activated cancer therapy
Minerals CaCO3 Tritc-dextran Parakhonskiy et al. (2013), fluorescent dye Rhodamine 6G Parakhonskiy et al. (2012a) catalase, insulin, aprotinin Feoktistova et al. (2020) Detection and release functionalities
Alginate hydrogel Muderrisoglu et al. (2018) Loading of active enzymes
PAH, PSS Sergeeva et al. (2015)
Ca3(PO4)2 Poly acrylic acid (PAA) Wang et al. (2017) pH-responsive drug-release vehicles
Hydroxyapatite Pam78 Zaheer et al. (2006) NIR detection by bisphosphonate derivative
Poly (ε-caprolactone) (PCL) Ji et al. (2020b) Improving cytocompatibility and bio-compatibility
Hydroxyapatite, Wollastonite (WST)clay Potato starch (C6H10O5)n, Prabakaran et al. (2021)
SiO2, Au Perfluoropentane Li et al. (2018a) Stimuli-responsiveness, drug delivery and controlled release
SiO2 CD-PGEA Zhang et al. (2017)
Hyaluronic acid Gupta et al. (2018)
Pyromellitic dianhydride (PMDA) Feng et al. (2019)
Poly (ethyleneglycol) N-(3-triethoxysilylpropyl)diethanolamine Climent and Rurack (2021) Fluorescence imaging
Clay Halloysite Hexadecyl trimethy-lammonium bromide (HDTMA) Tan et al. (2016) Stabilization
Alginate and chitosan Lisuzzo et al. (2019) pH-responsive drug-release vehicles
Polyethyleneimine (PEI), polystyrene sulphonate (PSS) Lvov et al. (2008); Tan et al. (2016) Drug release
Laponite Proteins, polymers Gaharwar et al. (2019) Targeted delivery wound healing, tissue adhesive
Semiconductor CdSe/ZnS, CdSe/CdS/ZnS Polyethylene glycol Sukhanova et al. (2022) Reduction of cytotoxicity
Carbons Multi-walled carbon nanotubes (MWCNTs) Hydrophilic moieties (MWCNT-OH, -COOH, -NH2, -SH) Kaufmann et al. (2017) Horseradish peroxidase, Ab2 (secondary antibody) BMIM·BF4 Cai et al. (2011) Specific anti-oncogene detection drugs carriers
Amphiphilic polycations (Poly (N-cetyl-4-vinylpyridinium bromide-co-N-ethyl-4-vinylpyridinium bromide-co-4-vinylpyridine)) (Sinani et al. (2005) Modification of aqueous dispersions
Carbon quantum dots (CQDs) Glucose oxidase, boronic acid, bis(3-pyridylmethyl)amine, β-cyclodextrin Huang et al. (2016); Feng and Qian (2018) folic acid Choi et al. (2014) Bioimaging with a high specificity
Fluorescent nanodiamond (FNDs) Glycosaminoglycans, Viral Envelope Proteins Pham et al. (2017) Targeted delivery and imaging
Fullerenes (C60) Cyclodextrins Ikeda (2013) Water-soluble fullerenes, photoinduced energy- and electron-transfer
Carbon nano onions glassy carbon electrodes (GCE) Polydopamine (PDA) Zuaznabar-Gardona and Fragoso (2018) pH detection with a high detection sensitivity over the pH range of 2–10
Graphene oxide (GO) PEG Xu et al. (2014) poly (acrylamide) (PAA) (Xu et al. (2016) Reduction of cytotoxicity, improving drug delivery efficiency
Carbon nano onion clusters PEI, PEG Sun et al. (2019) Improving photothermal conversion efficiency
2.1 Stabilization 2.1.1 The meaning and theory behind colloidal stabilization

Colloids are referred to as a system consisting of nanoparticles with the sizes from 10 nm to ∼1 μm dispersed in a fluid, most frequently the liquid phase. The Derjaguin–Landau–Verwey–Overbeek (DLVO) theory can quantify effectively the colloidal stability, but it can only work for aqueous solutions containing simple electrolytes. Briefly, the balance of attractive van der Waals (vdW) (Figure 5A) and repulsive forces caused by the electrostatic double layer (EDL) (Figure 5B) determines the colloidal stability in an aqueous suspension. Actually, besides vdW and EDL, steric repulsion (Figure 5C) inherent to macromolecules such as synthetic polymers or proteins could dramatically enhance the colloidal stability due to osmotic pressure and elastic recoiling effects (de Gennes, 1987). Of course, there are other forces needed to be taken into consideration, like depletion forces and magnetic forces controlled by an extra electromagnetic field (Petry et al., 2019; Espinosa et al., 2020). The study showed that fullerenes can be water-soluble and have a high stability achieved by host-guest interactions with cyclodextrins (Ikeda, 2013). It should be noted that taking into account the energy-distance curves, it would be possible to predict the behaviour of colloids. One example, aqueous solutions containing simple electrolytes, is shown in Figure 5D.

Schematics of colloidal interactions (A–C) and illustration of potential energy-distance curves describing colloidal interactions (D) (Moore et al., 2015).

Despite significant breakthroughs in biomedical applications of nano- and micro-particles, the gap between research and their translation into clinics is still significant (Venditto and Szoka Jr, 2013). One of the primary challenges is the complexity of the system, while one should not exclude the lack of understanding of all mechanisms governing particle interactions and effects on biological objects, especially when they are immersed in a complex cellular environment (Moore et al., 2015). In part, this is because the actual system and environment including cell surface, extracellular matrix, and cell culture medium are quite complex compared to commonly used cell culture media like DMEM, MEM, and PBS solution. Most of the particles are taken up via active endocytosis, during which they are exposed to different conditions, like pH changes from 7.4 (in the extracellular medium) to 5.5 (in late acidified endosomes) to 4.5 (in endolysosomes). Moreover, endolysosomes are rich in hydrolytic enzymes that can affect/dissolve the entire NPs or their coatings. Internalized AgNPs were reported to degrade quickly into Ag+ when immersed in endolysosomes (Foldbjerg et al., 2015). Besides, behaviour of particles is sensitive to the ionic strength of the solution. For example, calcium carbonate (CaCO3) can recrystalize in hydroxyapatite (Ca10(PO4)6(OH)2) in cell medium, which contains the PO4 3− groups or aggregate in the presence of sodium/chloride ions (Na+/Cl−) (Parakhonskiy et al., 2012b) as well as crystalize and dissolve at relatively acidic pH values inside the cell (Abalymov et al., 2018).

Affected by the dynamic complex nature of the cellular environment, the loss of colloidal stability of particles would likely lead to colloidal aggregation into larger and irregularly shaped clusters and even dissolve entirely or stimulate recrystallisation or structural changes. The poor stability of colloids would lead to misrepresentative results or low reproducibility and, at the same time, influence their biodistribution, pharmacokinetics and systemic toxicity (Moore et al., 2015). Another problem is the corona effect which requires additional stabilization. This is because when nanoparticles are injected into the intravenous stream, the blood’s proteins would adsorb on the surface of the particles, thus forming a protein corona layer (Lee, 2021). Protein corona may lead to undesirable effects, for example, facilitating or inhibiting cellular uptake and mitigating or stimulating the immune response (Del Pino et al., 2014; Mosquera et al., 2018; Liu et al., 2020a). To guarantee that nanoparticle functions remain as stable as possible, organic molecules like PEG (Poly (ethylene glycol)), PAA (Poly (acrylic acid)) (Tambunlertchai et al., 2017; Xiao et al., 2020), nanocelluloses (Kaushik and Moores, 2016) are commonly reported to be added as stabilizing agents during the formation process.

 2.1.2 Approaches to stabilize inorganic colloids

One of the most widely and effectively accepted strategies to enhance colloidal stability is to avoid particle aggregation via surface modification (Albanese and Chan, 2011), involving for example steric and electrostatic stabilization (Bihari et al., 2008; Liu et al., 2021). Table 2 juxtaposes these three methods used to stabilize the inorganic particles illustrated with respective organic molecules.

The methods used to stabilize inorganic colloids via organic molecules.

Stabilization method Inorganic NPs Organic molecule Medium Reference
Electrostatic interaction Au, Ag Citrate coating DMEM + 10%FBS, water Casals et al. (2011); Wen et al. (2020)
CaCO3 Vitamin D3 Edible oil-in-water Pickering emulsion Guo et al. (2021)
SiO2 N-(6-aminohexyl)-3-aminopropyltrimethoxy silane PBS, TRIS buffer, DMEM + 10%FCS Graf et al. (2012)
Steric Au Thiolated PEG, amphiphilic block co-polymer (PVA-COOH) Phosphate buffer with lysozyme, water (Zhang et al., 2009; Wen et al., 2020)
Gallic acid 2.5 mM glucose Kim et al. (2017)
SiO2 Poly (methyl methacrylate) (PMMA) 1-alkyl-3-methylimidazolium-based ionic liquids Singh et al. (2019)
PEG TRIS buffer, DMEM + 10%FCS Graf et al. (2012)
Perovskites hydrolyzed poly (methyl methacrylate) (h-PMMA), poly (ethylenimine) (PEI-25K) Polar solvents (methanol) Jiang et al. (2021)
Electrostatic Au Thiolated DNA 0.1 M NaCl Mirkin et al. (1996); Lee et al. (2021)
PEI/siRNA/PEI 10 Mm NaCl Elbakry et al. (2009)
PMPC (poly methacryloyloxyethyl phosphorylcholine) Serum and lung lavage fluid King and Fiegel, (2022)
CeO2, γ-Fe2O3 PAA DMEM, RPMI-1640 + 10%FBS Chanteau et al., (2009); Safi et al., (2011)
Au, Ag, Fe3O4, CoO, CeO2 FBS coating (10%) complete cell culture medium (cCCM) Casals et al. (2011)
Fluorescent nano diamond Protein polymers C4−K12 (polypeptide) NaCl solution (at least 1 M) Zheng et al. (2017)
CdTe, CdSe/ZnS chitosan Queous solution (pH 5.6) Slyusarenko et al. (2019)
CaCO3 ALP, Alginate PBS, 0.9 M NaCl Abalymov et al. (2020)
2.1.2.1 Electrostatic interaction

When NPs are exposed to a cell medium, colloidal interactions take place at the surface of particles (in the surrounding medium). The overall ionic strength of the new-mixture system determines the EDL fate. Typically, low ionic strength enlarges ion clouds extending further from the particle surface, which diminishes or resists particle-particle interaction. In contrast, an environment with a high ionic strength will suppress the EDL and enforce the attractive vdW leading to NP aggregation (Edwards and Williams, 2004). Electrostatic stabilization is generally reported to be poor in cell culture media (Moore et al., 2015).

 2.1.2.2 Steric stabilization

Steric stabilization is the universal method to reinforce colloidal stability. This is often achieved via natural macromolecules (e.g., chitosan, alginate) or synthetic polymer coatings, e.g. PVA (polyvinyl alcohol), PEG (polyethene glycol) (Zhang et al., 2009). Based on numerous studies, there are two ways to make the system more stable: a) coat the NPs with an uniform monolayer of macromolecules, which could provide extra robust steric stabilization, and b) prevent the proteins from attaching to NPs surfaces, which paves the way for bridging effects and leads to aggregation. This is because proteins contained in the cell culture media could cover the surface of particles forcing proteins to interact with more than one NP and facilitate aggregation (Biggs et al., 2000). It has been also shown that the effects of PEG molecules on AuNPs’ colloidal stabilization depend on their molecular weight and concentration (Zhang et al., 2012b).

 2.1.2.3 Electrostatic stabilization

One approach to improve colloidal stability is electrostatic stabilization which combines the effects of electrostatic and steric stabilization. In this case, macromolecules strongly coat the NP surface as a physical barrier and therefore impede proteins attaching to NPs’ surfaces. Meanwhile, these charged macromolecules would provide repulsive static electricity given that the environment of the cell culture medium is usually weak alkaline and negatively charged; the charge on NPs can be negative through functionalization by, for example, poly (acrylic acid) (PAA) (Chanteau et al., 2009) or it can be positive (for example, DMAP).

It should be noted that the interactions between the colloidal particles and the capping agents are sophisticatedly complex and depending on media, NPs, functional ligands, iron strength, etc. To interpret and mimic the relation of the colloidal and biological media precisely in vitro, there is still significant needs and that largely depends on interdisciplinary efforts to be made in materials science, cell biology, pharmaceutics, biophysics, etc.

 2.2 Controlled loading and release

One of the most feasible ways to enhance the drug efficacy is to load a suitable amount of drug and release it at the lesions. The hybrid nanocomplex is a powerful tool to modify drug loading and optimize release behaviour (Li et al., 2017). The porous inorganic particles are frequently used as drug carriers. Functionalizing them with additional polymer layers improves the stability and contributes to controlled release mechanisms. For example, the functionalisation of porous CaCO3 particles with polymer layers would stabilize the containers on hour-, week-, even months scales, leading to a prolonged drug release. APTES-modified halloysites have a higher loading capacity and were shown to prolong the release of ibuprofen (Tan et al., 2016). The drug delivery system release behavior based on metal-organic framework (MOF) like MIL-101(Fe)-NH2 could be modified by long-chain polyamines (Almáši et al., 2018). Zhou etc., designed a pH-triggered self-unpacking capsules consisting of a MOF and zwitterionic hydrogel coating (Zhou et al., 2021). The MOF core with a large pore size and surface guarantees high loading efficiency. The outer layer of hydrogel is made of pH-sensitive poly-Eudragit L100-55, which would dissolve at a pH > 5.5 and therefore protect the oral peptide drug from degradation when passes through an acidic gastrointestinal environment and is released in the intestinal fluid. Multi-walled carbon nanotubes functionized by hydrophilic organics might be explored as an efficient nanotransporters for oligodeoxynucleotide (Kaufmann et al., 2017). The nanohybrid graphene oxide (GO)-PEG/paclitaxel (PTX) shows relatively high loading capacity for PTX (11.2 wt%) and existed significantly higher cytotoxicity to human lung cancer A549 and human breast cancer MCF-7 cells compared to free PTX (Xu et al., 2014). Loading and release may differ for various drug deivery carriers, and in this regard polyelectrolyte multlayer nano- and micro-capsules are attractive carriers (Li et al., 2022b), which are composed of polyelectrolytes (organic molecules), but their functionalization with such inorganic particles as gold (Skirtach et al., 2005) or silver (Skirtach et al., 2004; Radziuk et al., 2007) allows to perform release.

 2.3 Reduction of cytotoxicity and improvement of biocompatibility

There have been reports on drugs providing undesirable toxic effects (Hirt and Body-Malapel, 2020). Due to the EPR effect, the clearance of NPs rates from circulation streams and tissues is much lower, and it would result in the accumulation of NPs at the surface of the tissue or within cells and pose the risk of disruption of organelle integrity or gene alterations (Gitipour et al., 2016). The toxicity of NPs is highly correlated with their complexity and diversity in terms of size, shape, charge, production methods, chemical composition, surface functionalization, and aggregation (Lewinski et al., 2008; Lv et al., 2021; Nitti et al., 2022). In order to improve inorganic NPs safety, organic protective layers or coating agents are usually used to cover their surface, which would help to prolong the circulating half-life and minimize the reticuloendothelial system uptake (Nie, 2010; Rabie et al., 2019). Recent study found that when AuNPs are coated with ferritin, their biocompatibility is dramatically enhanced as the cellular uptake of transferrin-receptor-rich cell lines increased more than seven times and showed very low toxicity on different human cell lines (Moglia et al., 2021). It was reported that biocompatibility of graphene oxide could be enhanced by PEG, PAM, and PAA (Xu et al., 2014; Xu et al., 2016).

 2.4 Targeted delivery

The lack of efficient delivery systems has impeded the efficiency of drugs, especially for small molecule drugs for chemotherapy which are always accompanied by noticeable side effects (Mu et al., 2020). In order to take the best advantages of drugs, various materials such as lipids, polymers (Go and Leal, 2021), hydrogels (Lengert et al., 2017), metal-organic framework (MOF) (Zhou et al., 2021; Kiadeh et al., 2021) and NPs (Jun et al., 2008; Xie et al., 2012; Biju, 2014; Tarakanchikova et al., 2020) have been exploited. Also recently, SiO2 (Gupta et al., 2018), Fe3O4 (Liu et al., 2020b), CaCO3 (Huang et al., 2022), and AuNPs (Sharifi et al., 2019) have been investigated extensively as emerging delivery carriers. Especially, AuNPs have many advantages, such as simple synthesis, easily tunable size, chemically inert, oxidation-free, facile surface modification, and versatile conjugation with biomolecules (Kang et al., 2019). Organic molecules can be used for functionalization of AuNP targeting specific drug delivery routes with the LbL method. For example, Lee etc., designed the nanocomplex-AuNPs/siRNA/polyethyleneimine (PEI)/hyaluronic acid (Ha) modified by cysteamine, which could target specific intracellular delivery of siRNA via Ha receptor-mediated endocytosis (Lee et al., 2011). CaCO3 has proved to be useful for intracellular delivery through its crystal phase transition (Parakhonskiy et al., 2013). Recently, sub-micro vaterite CaCO3 particles loaded with photosensitizer drug porphyrazine (pz) was found to mainly accumulate in the tumor blood vessels, and the tumor uptake of pz was enhanced by 1.8 times; while loaded gold nanorods improved delivery by 3.4 times, showing extensive potential to be explored as tumor therapeutic agent for photodynamic therapy (Parakhonskiy et al., 2021).

 2.5 Detection

Plasmonic nanoparticles like AuNPs and AgNPs, exhibit distinct colours throughout the visible and near-infrared regions due to their localized surface plasmon resonance (LSPR) absorption and scattering (Mulvaney et al., 1992; Qin et al., 2015; Kang et al., 2019; Cui et al., 2020), and have been used in applications in sensing, energy, catalysis, and biomedicine (Lin et al., 2016; Vita et al., 2018; Dai et al., 2021; Song et al., 2021). LSPR provides a higher detection accuracy than traditionally used surface plasmon resonance (SPR). SPR emanates from coherent oscillations of conduction electrons caused by electromagnetic radiation excitation at the surface, because the size of NPs is comparable to the mean free path of electrons in these metals, which restricts the plasmon to NPs. Besides the LSPR, plasmonic nanoparticles (for example, AuNPs and AgNPs) can be also used for surface-enhanced Raman scattering (SERS) sensing, which could dramatically improve the detection sensitivity by 102 to 1014 times (Yashchenok et al., 2012; Lengert et al., 2018). When plasmonic nanoparticles are combined with specific aptamer, antigen-antibody recognition, enzyme etc., they could be modified as a specificity detection platform (Figure 6).

A schematic overview of mechanisms for plasmonic NPs-based biosensors for detection and their applications.

Magnetic NPs possess special effectsf, for example, Yang reported a combinination of polydopamine (PDA), GE11 peptide and ultra-small superparamagnetic iron oxide NPs, GE11-PDA-Pt@USPIOs which have a high specificity for EGFR-positive tumor cells; that would be used in radio-chemo combination therapy, in which such NPs enhanced magnetic resonance imaging/photoacoustic imaging (MRI/PAI) (Yang et al., 2019). Zhu et al. (2021) explored a selective and sensitive detection platform for Staphylococcus aureus by coating the AuNPs with polydimethylsiloxane (PDMS) film. But, it should be noted that the plasmonic NPs would lose plasmonic functionality once NPs dissolve. So one of the most critical aspects in designing and exploring the detection tools based on the plasmonic nanoparticles is to find suitable stabilizers. Commonly used stabilizing agents and size controllers include the following molecules: cetyltrimethylammonium bromide (CTAB), citrate, PVP, PEG (Kang et al., 2019). Surface plasmon resonance imaging (SPRi) was used for label-free detection based on plasmonic NPs (Guner et al., 2017). The detection platforms based on gold and silver NPs can be used to analyze many types of samples, including small organic molecules (Liu et al., 2011), nucleic acids (Thaxton et al., 2006), proteins (Anfossi et al., 2019), sugars (Brasiunas et al., 2021), cells (Zhang et al., 2010), bacteria (Li et al., 2022a), cations and anions (Liu et al., 2011; Dutta et al., 2019), etc.

Besides plasmonic nanoparticles, carbon quantum dots (CQDs) represent an emerging fluorescent nanomaterial which was used in various applications, especially in chemosensing and biosensing (Ding et al., 2014; Nekoueian et al., 2019). When they are functionalized by suitable organic molecules, they can be used as a versatile detection platform that includes small bioactive molecules like Vitamin B2, amino acids, big molecules (DNA, RNA), enzymes, or cells. When CQDs are functionalized by folic acid, a biomarker for cancer, hybrid nanoprobes could target cancer cells due to their high affinity to folate receptors (Feng and Qian, 2018).

 2.6 Other applications outside of biomedicine

Hybrid nanocomposites based on inorganic NPs with organic molecule modifiers have various functions covering a wide range of applications, particularly in the following sectors and applications: health sector (Byrappa et al., 2008; Kopecek, 2009; Chanana et al., 2013; Ni et al., 2020; Lavrador et al., 2021), wound healing applications (Chen et al., 2022), long-term tracking stem cell transplantation therapy in vivo (Xie et al., 2022), electrochemical immunosensing (Campuzano et al., 2017), optics (Shavel et al., 2004; Melnikau et al., 2016; Melnikau et al., 2018), micro-electronics (Banerjee et al., 2009), transportation, packaging (Moustafa et al., 2021), energy (Li et al., 2016; Mahmood et al., 2016; Liu et al., 2019), housing (Saba et al., 2016), catalysis (Shahmoradi et al., 2011; Liu et al., 2014; Tomai et al., 2021) and the environment (Sanchez et al., 2011). Cyclodextrins (CDxs) were reported as solubilizing agents, which could improve C60 water solubility when coated by CDxs (Ikeda, 2013).

TiO2 based bio-catalytic nanoparticles modified by 2, 2′-Azino-bis-(3-ethyl benzothiazoline-6-sulfonicacid) (APTES), glutaraldehyde (GLU) and laccase possess a high degradation rate for such micropollutants as bisphenol-A (Hou et al., 2014) A wide-range and fast response solid-state potentiometric pH sensors based on PDA coated carbon nano-onion (CNO) electrodes were reported (Zuaznabar-Gardona and Fragoso, 2018). PDA films endow this system with a fast response toward pH changes, while CNO is responsible for transferring the signal quickly due to its large surface area and electrochemical properties. This pH sensor could work in the range from 2.2 to 8.3. Ji et al. (2020a) found that silk fibroin (SF)/Bi2O2CO3-Cu2O nanofibers produced by electrospinning can be easily recycled and have excellent photocatalytic and antibacterial activities, and low-cytotoxicity, which paves the way to promoting their practical applications in, for example, water treatment. This is because SF has a large surface to immobilize powder Bi2O2CO3-Cu2O photocatalysts, and the hybrid mat-like structure separates itself from water efficiently. The nanocomposite coating – polyurethane (PU)/SiO2-Al2O3 - showed significant resistance against corrosion compared to that of pure steel (Xavier, 2021).

 3 Inorganic surfaces functionalized by organic molecules

Typically in the field of biomedicine, organic coatings provide the same functionalities as those described above for colloids, except for such applications as targeted delivery, which involves the movement of an inorganic object by itself. In Figure 7, selected inorganic surface functionalization modalities via organics are shown. Table 3 summarizes modifications of representative inorganic surfaces by organics highlighting their applications and gained functionalities. In the following part, the role of organic molecules is illustrated mainly for metallic and inorganic (non-metallic) materials.

Functionalization of inorganic surfaces by organic molecules. Metal (AFM images of TiO2 coated by alginate hydrogel coatings reproduced from (Muderrisoglu et al., 2018) with permission Wiley-VCH), Carbon (optical and SEM images of the graphene oxide modified by polyethyleneimine film; reproduced from (Nam et al., 2016) with permission of ACS), Clay (SEM images of the Poly(vinyl alcohol)/synthetic hectorite film cross-section with a thickness of 4.3 μm (Teepakakorn and Ogawa, 2021) with permission of the Mater. Adv.), Ceramic (SEM images of the poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) (Mehdikhani-Nahrkhalaji et al., 2015) reproduced from Dent. Res. J. (Isfahan)).

Overview of hybrid organic films/coatings on inorganic substrates/flat surfaces, their composition and functionalities.

Hybrid flat surface composition Functionalities and applications
Inorganic flat surface Organic films/coatings and reference
Alloy SS-Ti Stent Phosphorylcholine (PC) (Huang et al. (2014b) Load and release drugs by stimulation corresponding
Co–Cr Stent BioLinx (hydrophobic C10,hydrophilic C19, polyvinyl pyrrolidone) (Huang et al. (2014b)
PC Huang et al. (2014b)
Pt–Cr Stent PLGA, CE approved
SS stent Polyethylene-co-vinyl acetate (PEVA) FDA approved Load and deliver drugs, improve the hemocompatibility, modify cells adhesion, proliferation, and migration behaviour, improve stainless steel (SS) stents extrusion resistance
Polydopamine (PDA\) Lee et al. (2007); Yang et al. (2012)
Ni-Ti Stent anti-CD34 antibody Sun et al. (2021a) Better blood compatibility, Promote cell migration, adhesion and proliferation
Vascular endothelial growth factor (VEGF) Sun et al. (2021a)
PDA Sun et al. (2021a)
Ti-6Al-4Vscaffolds PDA Li et al. (2015)
2024 Al alloy PEI/PSS, inhibitor (benzotriazole) Zheludkevich et al. (2007) Active corrosion protection, self-healing property
AZ91 Mg alloy 3-glycidoxypropyl)-trimethoxysilane (GPTMS) (Chen et al. (2020), poly (ethylene imine) (PEI)/poly (acrylic acid) (PAA), fluoropolymer (poly (vinylidene fluoride), PVDF) Zhang et al. (2021a)
Ceramic Bioactive glass/ hydroxyapatite (HA) Poly (lactide-co-glycolide) Mehdikhani-Nahrkhalaji et al. (2015) Realize tunable and sustained release of growth factors or drug), improve mechanical integrity, improve targeted cells attachment, proliferation, and bioactivity
Bioactive glass Chitosan Uskoković and Desai (2014)
Hydroxyapatite (HA) PDAM Cai et al. (2014)
PDA/PLL Han et al. (2019)
Perovskite PEG Fu et al. (2019) Improve the stability of perovskite solar cells
CaCO3 Alginate hydrogel Muderrisoglu et al. (2018) Loading active enzyme
Clay synthetic Na + -saponite (Kunimine Industries Co. Ltd.) Sodium polyacrylate Tetsuka et al. (2007) Enhance the thermodynamic stability, transparency of clay films
Synthetic saponite, stevensite Functional polymers, dye molecules, protein molecules Zhou et al. (2011) Catalysis, modified electrodes and optoelectronic devices, anti-corrosion and packaging materials
Iron coated montmorillonite clay (FeOx-MMT) Gallic acid Levy et al. (2020) Improve the surface redox reactivity
Synthetic hectorite (SWF) Poly (vinyl alcohol) (PVA) (Teepakakorn and Ogawa (2021) Self-healing property, improving the adhesive ability to substrates
Carbons Fullerene (C60) PEG Fu et al. (2019) Enable fullerenes to become amphiphilic
Graphene oxide Branched polyethene-imine Nam et al. (2016) Enhance graphene oxide ultra thinness membranes stability
PEI Zhang et al. (2021b) pH-responsive corresponding, improved the hydrophilicity

SS, stainless steels; SS-Ti, stainless steels-Titanium alloys; Pt–C,r Platinum- Chromium alloys; Ni-Ti, Nickel- Titanium alloys; Co–Cr, cobalt-chromium alloys.

Functionalization of soft hydrogel-like films composed of poly-L-lysine and hyaluronic acid by inorganic nanoparticles has been shown to extend their application range (Skirtach et al., 2010; Volodkin et al., 2012), while their functionalization by capsules with nanoparticles allows to perform remote release (Volodkin et al., 2009).

3.1 Challenges in regard with clinical applications of biomedical materials

Metallic biomaterials are essential for development and implementation of clinical implants to reconstruct failed tissue, especially failed hard tissue (Basova et al., 2021). Around 70%–80% of implants are made of metallic biomaterials; among which the most representative clinically used metallic biomaterials are stainless steel (SS), cobalt-chromium (Co–Cr) and titanium (Ti) alloys (Niinomi et al., 2012). Even though metallic materials have been widely used, there are still many obstacles that impede broad clincal applications of implants once and for all time, especially for long-life implantations. The common problems are mainly identified as follows (Abdel-Hady Gepreel and Niinomi, 2013):

1) mismatch of mechanical properties (Figure 8): this impedes cell attachement to the surface of the implant and leads to fibrous encapsulation at the site. Potential solution: Modification of mechanic properties and facilitation of cell attachment by organic molecules or coatings;

2) corrosion: show low fatigue strength and are vulnerable to corrosion, leading to metal ions or monomer release into the body and may damage the surrounding cell tissue. Potential solution: Application of anti-corrosion coatings;

3) lack of cell biocompatibility: allogeneic transplantation may trigger an immune response with serious side effects such as inflammation. Potential solution: Loading and covering with biocompatible polymers and growth factors.

Mechanical properties (the Young’s modulus) of natural bone materials in comparison with those for other materials often used in biomedicine; data are based on (Orlovskii et al., 2002) and (Butscher et al., 2011).

Polymers: (PCL: poly (caprolactone), PE: polyethene, PUR: polyurethane, PMMA: poly (methyl methacrylate), POM: Polyoxymethylene, PLA: Polylactic acid, PEEK: polyetheretherketone), Metals: (TA: Titanium-based alloy, TTA: Tantalum based alloy, SS: stainless steels, CoSA: Cobalt-based super alloy), Ceramics (CaP: Calcium phosphate bio-ceramic, HA: hydroxyapatite based bio-ceramic, BG: Bioglass based bio-ceramic, ZrO2: Zirconia based bio-ceramic, MgO: Magnesia based bio-ceramic, Al2O3:Alumina based bio-ceramic).

 3.2 Optimization of mechanical biocompatibility

There are two strategies to optimize the material’s mechanical biocompatibility. One strategy is towards modifying its element and structural composition from the inside. With addition of a small amount of graphene to chitosan (0.1–0.3 wt%), the hybrid graphene/chitosan films’ elastic modulus was increased by ∼ 2 times compared to that for pure chitosan (Fan et al., 2010). Taking bone repair engineering as a representative example, bone is a natural hybrid material consisting of two major parts: soft inner cancellous and hard cortical shell (Wubneh et al., 2018). Around 70% of it is composed of inorganic hydroxyapatite (HA, Ca10(PO4)6(OH)2), which is a member of the calcium phosphate (CaP) mineral family (Pal, 2014) and the rest (20%–30%) is extracellular organic matrix—a mixture of water, collagenous and non-collagenous proteins. In contrast, only around 2% is made of bone-resident cells (Belinha, 2014). Inspired by the sophisticated composite structure of bone tissue and clinical trials, the strategies of developing hybrid composites used to boost bone repair have become a hot topic.

The other one resorts to the surface modification and function by films or coatings to facilitate the attachment of cells to the surface of materials and to stimulate cell proliferation and differentiation (Miyazawa et al., 2008; Glazebrook et al., 2013; Ho-Shui-Ling et al., 2018). Yang et al. (2021b) found that the Ti-based implants could obtain dual function: antibacterial properties and facilitation of osteointegration in vivo when hyperbranched poly-L-lysine is grafted on its surface. In the area of stents, Sethi and Lee reported a successful strategy to design the combo stent where the stainless steel surface was coated by anti-human CD34 antibodies intermediated by a polysaccharide (Sethi and LEE, 2012). This combo stent showed excellent endothelial progenitor cell adhesion capability from the circulating system with the antibody coatings (Figure 9). In bone repair engineering, composites like collagen/HA, β-TCP/collagen, HA/Starch, HA/gelatin, and PCL/HA are frequently reported for surface modification (Butscher et al., 2013; Ruiz-Aguilar et al., 2017; Ho-Shui-Ling et al., 2018; Prabakaran et al., 2021). It was described that hydrogel coatings loaded with active enzymes coated on top of a titanium plate could significantly stimulate osteoblast colonization and growth (Muderrisoglu et al., 2018). It was recently shown that introduction of poly-hydrobutyrate (PHB) enables piezoresponse of CaCO3 mineralized 3D scaffolds, which can be used for local delivery of bioactive molecules and for enhancement of tissue repair (Chernozem et al., 2022).

Surface functionalization of a stent by antibody coatings (Sethi and LEE, 2012) with permission of the Wiley Online Library.

Table 4 provides summary of hybrid bone scaffolds, their components, and working mechanisms.

List of commercial products with organic bioactive molecules (growth factors, peptides or small molecules) and inorganic or hybrid material carrier and their stage of development in the bone scaffolds.

Product name (company) Inorganic content Organic content Application Stage Mechanism of action References
Augment® Bone Graft Wright (Medical Group) β-TCP (powder) rhPDGF-BB (solution) Hindfoot and ankle fusion surgery M rhPDGF-BB attracts Mesenchymal Stem Cells (MSCs) to the local fusion site and stimulates its divide, proliferation as well as promotes revascularization; The β-TCP component fills the surgical defect, reliably delivers the rhPDGF-BB over time, and provides a physical scaffold for new bone formation DiGiovanni et al. (2013); DiGiovanni et al. (2016) https://www.augmentbonegraft.com/healthcare-professionals/clinical-evidence/
Mastergraft Matrix ext, Mastergraft Strip (Medtronic) biphasic calcium phosphate (β-TCP and HA) bovine type 1 collagen Bone voids or gaps filler M Mastergraft mimics human cancellous bone, which could be resorbed controlled and enhance osteoconductivity and vascularization without an immune response https://global.medtronic.com/xg-en/healthcare-professionals/therapies-procedures/spinal-orthopaedic/bone-grafting/evidence/mastergraft.html
NucleostimNeovasculgen (NextGen Company Limited) Octacalcium phosphate (OCT) naked plasmid DNA carrying the vascular endothelial growth factor (VEGF) gene Lumbar spine, Cervical spine, foot and ankle fusion P- II Plasmid DNA with VEGF gene to induce VEGF secretion by cells and promote angiogenesis; OCT as a possible precursor with extraordinary osteoconductive capacities could facilitate osteogenic cell differentiation and treated as effective scaffolds for cell delivery NCT03076138 Bozo et al. (2021)
Amplex (Ferring Pharmaceuticals) ß-TCP, HA B2A (Powder) Indicated for ankle or hindfoot arthrodesis P- III B2A is a synthetic multi-domain peptide augmenting osteodifferentiation via increasing endogenous cellular bone morphogenetic protein two by preosteoblast receptor modulation at the local arthrodesis site ß-TCP(80%), HA (20%) granules are used as a bone void filler (BVF) NCT01224119, Glazebrook et al. (2013), https://clinicaltrials.gov/ct2/show/study/NCT03028415
i-FACTOR Bone Graft (Cerapedics) inorganic bone mineral small peptide P-15 Bone Graft IDE, CE Mark i-FACTOR Bone Grafts attract osteogenic cells, which then attach to p-15 and activate bone a natural hydroxyapatite ABM Arnold et al. (2016), https://cerapedics.com/comparative-performance NCT01618435, NCT02895555

IDE: large human clinical study.

 3.3 Anticorrosion protection

One of the most successful applications of coatings is anticorrosion protection. Recently, various groups developed advanced smart coatings which were made not only from the polymer layer protecting it from oxygen and aggressive ions, but also from intelligent delivery systems containing carriers with corrosion inhibitors. For example, the degradation of the organic part allows to release inhibitor and provides a self-healing effect to the damaged place (Zheludkevich et al., 2007; Deng et al., 2021).

The most remarkable breakthroughs occured frequently in fully-erodible drug-eluting stents (EDES). Among the top three studied biodegradable metals (magnesium, iron, zinc), magnesium and its alloys are advancing to commercial products (Huang et al., 2014b; Zheng et al., 2014). This is because mechanical properties of magnesium are closer to the natural bone, which can dramatically minimize the stress-shielding effect–the biggest issue with non-degradable implant materials such as stainless steel and titanium alloys (Abdel-Hady Gepreel and Niinomi, 2013). However, magnesium alloys usually corrode too quickly in the human body and play a supporting role. Hybrid coatings improved their degradation resistance significantly, as Figure 10 shows (Rahman et al., 2021). Al Zoubi et al. (2020) also presented a successful strategy to enhance its corrosion resistance via organic coatings made up of 2-mercaptobenzimidazole (MBI). In 2016, Magmaris, a biodegradable and resorbable stent (BRS), was produced by biotronic, a German medical device company that obtained certificate approval in Europe. This remarked the first metallic BRS that became available on the market (Rapetto and Leoncini, 2017). It consists of a Mg alloy backbone and biodegradable poly-l-lactic acid (PLLA) coating, which could load sirolimus. Within the last 2 years and following-up clinical data published in May of 2021, it was reported for BIOSOLVE-IV that target lesion failure (TLF) of Magmaris is 6.6% (71/1,075 patients) and without scaffold thrombosis after 12 months of implantation, confirming its long-term safety.

Comparison of the degradation of (A) pure Mg, (B) Hydroxyapatite on Mg, (C) Silk fibroin + hydroxyapatite on Mg, after immersion in Hank’s solution for 7 days, (D) Schematic illustration of the protection coating on Ma alloy (Rahman et al., 2021), with the permission of the ACS.

 3.4 Immune response and inflammation treatments

Organic coatings or films are explored extensively as drug and growth factor carriers to optimize implant performance and reduce or prevent the high potential risks and side effects like those mentioned above. Some representative applications are drug-eluting stents (DES), while another is bioresorable scaffolds (BRS). They comprise metal body and polymer coatings, often used in cardiovascular stents. Polymer coatings are responsible for loading and delivering drugs, such as sirolimus and paclitaxel (Garg and Serruys, 2010; Papafaklis et al., 2012; Iqbal et al., 2013). Taking three kinds of evaluated clinical Zotarolimus-eluting (ZEs) stents as a reference, a comparison between ZESs is summarized in Table 5. It can be noticed that the drug release profiles could be modified by altering the composite of metallic platforms or polymeric coatings.

Representative ZEs comparison.

Stents brand Platform Polymer coating Drug (zotarolimus) release TLR%
Endeavour Co–Cr PC 95% released in half month 5.1
Resolute Co–Cr Hydrophobic C10, hydrophilic C19, PVP 85% elutes in 2 months 1.1
ZoMaxx SS-Ti PC 90% released in 1 month 9.4

TLR, target lesion revascularization at 1 year, p b 0.001 (Miyazawa et al., 2008).

In bone repair engineering, Yang reported a successful strategy to make bipolar metal flexible fibrous membranes based on MOFs(ZIF-11 and HKUST-1), acting as carriers and achieving sustainable release of bone regeneration factors such as Cu2+, Zn2+ (Yang et al., 2022). This flexible fibrous membrane has been verified in regard with multiple tissue synchronous regeneration at the damaged tendon-to-bone interface, like tendon and bone tissue repair as well as fibrocartilage reconstruction (Figure 11).

Schematic illustration of hybrid nanofibrous membrane fabrication and the effect of regulating the synchronous regeneration of the bone-tendon interface by metal ions released from the nanofiber in situ (Yang et al., 2022) with the permission of Wiley Online Library.

Some antagonistic but complementary properties of organic and inorganic materials are summarized in Figure 12, which is useful for designing or optimizing hybrid materials with appropriate properties.

Antagonist (yin-and-yang), but complementary, properties of most common inorganic and organic compounds motivating their incorporation into hybrid materials.

 3.5 Other applications outside of biomedicine

Using organic films or coatings on the flat surface of the inorganics has accelerated the advancement in many areas, also outside of biomedicine. It includes protection and exploration of such materials as steel and copper, electrocatalysts (Yu et al., 2019), batteries (Li et al., 2018b; Wang et al., 2022) to advanced materials like sensors (Nugroho et al., 2018), wearable and flexible devices (Shim et al., 2008), marine ships, and aerospace vehicles (Mann, 2009; Huang et al., 2014a; Xu et al., 2021). Lee et al. (2007) reported polymer coatings synthesized from dopamine, which could coat virtually all types of material surfaces. Therefore, it could be used as a versatile platform for secondary reactions and to explore the coatings according to requirements necessitated by applications. A highly transparent flexible clay film has been obtained by organic polymer modification, which would be promising for display and other electronic devices (Tetsuka et al., 2007). A safer solid lithium battery was achieved by composite materials with polymer electrolyte (Wan et al., 2019). Teepakakorn and Ogawa reported that the poly (vinyl alcohol)-clay hybrid film has a high adhesive capability to substrates like glass and displayed self-healing soaking in water (Teepakakorn and Ogawa, 2021). Huang et al. (2019) summarized properties of organic and hybrid hydrophobic/superhydrophobic icephobic coatings for aerospace applications. PDMS-Ag@SiO2 core-shell nanocomposite antifouling coating was found to exhibit significant inhibitory effects on different bacterial strains, yeasts and fungi (Selim et al., 2018). Gu et al. (2020) reported the strategies to develop environmentally friendly marine antifouling coatings to protect ships from corrosion. The coating contains silicone polymer that prevents marine biological fouling on the ship’s surface by making it difficult for fouling organisms to adhere but facilitate removal after attachment.

Further, carbons can be functionalized with polymers. It was reported that introduction of branched polyetheneimine (bPEI) could enhance graphene oxide membranes’ stability and improve filtration efficiency (Nam et al., 2016). PEG provides fullerenes with amphiphilic properties, which enhance perovskite film quality and the perovskite solar cells’ stability (Fu et al., 2019). The utilization of PEI could make the pH-responsive graphene oxide a candidate for high-performance nanofiltration (Zhang et al., 2021b). Recently, hybrid conductive organic polymers like polyaniline, poly (dioxy-3,4-ethylenethiophene) and polypyrrole were used with traditional additive manufacturing materials like metals, paving the transition from 3D to 4D printing. Compared with traditional 3D, 4D printed material structures could response to external stimuli (voltage, force, heat), which is the core properties of soft-robotics or flexible wearable electronics (Martinelli et al., 2022).

 4 Conclusion

The recent decades have seen a dramatic rise and extensive developments in the areas of hybrid materials and their advanced applications. Hybrid materials composed of organic and inorganic constituents can be logically divided into two parts:

1) organic materials modified with inorganic constituents (inorganics-in-organics),

2) inorganic materials modified or functionalized with organic molecules (organics-on-inorganics).

In this review, we have described and analyzed organic molecule-modified inorganic material (organics-on-inorganics) compositions and their selected applications in biomedicine and other areas. According to the size and shape of the modified inorganics, organic molecule-modified inorganic materials (organics-on-inorganics), can be sub-divided into:

a) inorganic colloids and nanoparticles functionalized by organic molecules;

b) inorganic flat surfaces/matrices functionalized by organic molecules.

Incorporation of organic constituents is selected with a specific goal—to bring or complement properties not provided by inorganics, relevant for improving their stability and biocompatibility, reducing their cytotoxicity, enhancing corrosion resistance, providing organic molecule recognition, binding specificity, detection, loading and controlled delivery, release, etc. And as a matter of fact, in the field of biomedicine, organic molecules provide the same functionalities for inorganic colloidal particle and inorganic flat surfaces, perhaps with exception of applications like targeted delivery. Because targeted delivery of molecules involves movement of an inorganic object by itself. More specifically, in order to clarify the synergy of organics-on-inorganics, we have illustrated the roles of organic-inorganic hybrids in various applications.

Noble metals such as gold are chemically inert, but, in addition, they possess a high photothermal sensitivity and electromagnetic conductivity. The presence of such organic constituents as polymers, antibodies or macromolecules could be used for developing and designing targeted drug delivery vehicles and achieving multi-response drug release as well as real-time in situ detection. For traditional non-degradable metal implants like stainless steel and titanium (Ti) alloys, the surface-coated organic antibacterial and anti-inflammation drugs could dramatically reduce the risk of secondary surgery. For degradable metals like Mg and Zn, introduction of organic polymers could be used for controlling release profile to fulfil its function and implement fully-degradable drug-eluting stents (EDES), which would safely resorb in the body. Combining MOF with organics has pushed development of highly effective multi-drug loading and multistimuli release platforms, which is achieved via hydrogels and amino functional groups. In the area of magnetic nanoparticles like Fe3O4, complementarity of inorganic and organic materials is achieved through dual functionality: magnetic targeting (inorganic NPs) and biocompatibility enhancement (surface functionalization by biopolymers).

Such non-metal composite-like ceramics as CaCO3, Ca3(PO4)2, HA (Ca10(PO4)6(OH)2) have been extensively used in bio-medicine. It is not only because its porous crystalline configuration provides a higher loading efficiency compared to organic carriers like liposomes, but also due to its elemental composition, which provides Ca2+ necessary for remodelling. Introduction of small peptides, nucleic acids, and growth factors would contribute to optimizing bone grafts and circumvent potential immune response problems. This has been tested and used in commercial bone grafts. Clays, like halloysite (Al2Si2O5(OH)4), have also attracted extensive attention due to their atomically thin layered structure and charge characteristics. Their applicability can be enhanced by adding organic molecules. For instance, in drug delivery: combining clay NPs with organic polymers, targeted proteins or polysaccharides would be useful for enhancing biocompatibility, enabling targeting, and controlling release profile. Nano carbons, like carbon quantum dots, fluorescent nanodiamonds, fullerenes, and carbon nano onion are emerging biomedical materials due to their outstanding thermal and electrical conductivity, extraordinary fluorescent brightness and photostability as well as their low density and high strength. The presence of organic molecules such as oligosaccharides, peptides, and biopolymers would pave the way for accurate imaging diagnosis.

 5 Outlook

Although to-date developments have been very promising, innovations and breakthrough’s potential in the area of hybrid materials is yet to be fully realized. It is expected that higher levels of sophistication and miniaturization, environmental friendliness and lower production costs are expected to be achieved. Smart hybrid materials and devices will be further designed, synthesized and assembled showing excellent stimulus responses according to environmental changes based on the complementary yin-and-yang properties of organics and inorganics.

Taking as an example micro- and nano-hybrid material applications in biomedicine, the most obvious and key points are to open the “black box” of the interactions among hybrid materials with the organisms in real working situations lies in: setting-up construction strategies to synthesize the hybrids precisely with controlled stability, good biocompatibility, and excellent stimuli-responsiveness to various stimuli These smart hybrid materials would lead explorations toward such multifunctional platforms as soft-robot sensors in vivo, electrocatalysis, photoelectrocatalysis, wearable devices, and so on. Hybrid materials comprising organic coatings on inorganic materials are indispensable to combat modern threats such as antimicrobial resistance and nosocomial infections in general. The hybrid structure can endow the contact surfaces with specific (bio) functionalities keeping their mechanical integrity at a high level and, at the same time, providing controlled presentation of active compounds hosted/protected in organic part on demand.

A critical mass of interdisciplinary knowledge is needed for realization of this vision. To be more specific, the advanced characterization methods, emerging materials, and a collaboration of different research communities would dig out deep into the properties of hybrid materials and facilitate advanced materials applications.

 Author contributions

JS contributed to writing the first draft and made subsequent modifications. AV contributed to describing sub-subjects of this work, references, and provided contribution to the outlook. BP provided valuable suggestions for improving the framework of the review and the final draft. AS has organized work and led some of the research directions on which this work is based. All authors have read and agreed to the published version of the manuscript.

We thank the Special Research Fund (BOF) of Ghent University (01IO3618), FWO-Vlaanderen (G043322N; I002620N), and EOS of FWO-F.N.R.S. (project # 40007488) for support. JS acknowledges the support of the China Research Council (CSC, No. 202006150025). AV acknowledges financial support from the Staedtler Foundation in the frames of the project “Function by Design: Cellular Hybrids.”

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 References Abalymov A. A. Verkhovskii R. A. Novoselova M. V. Parakhonskiy B. V. Gorin D. A. Yashchenok A. M. (2018). Live-Cell imaging by confocal Raman and fluorescence microscopy recognizes the crystal structure of calcium carbonate particles in HeLa cells. Biotechnol. J. 13, e1800071. 10.1002/biot.201800071 Abalymov A. Van Poelvoorde L. Atkin V. Skirtach A. G. Konrad M. Parakhonskiy B. (2020). Alkaline phosphatase delivery system based on calcium carbonate carriers for acceleration of ossification. ACS Appl. Bio Mater. 3, 2986–2996. 10.1021/acsabm.0c00053 Abanades Lazaro I. Wells C. J. R. Forgan R. S. (2020). Multivariate modulation of the Zr MOF UiO-66 for defect-controlled combination anticancer drug delivery. Angewandte Chemie Int. ed. Engl. 59, 5249–5255. 10.1002/ange.201915848 Abdel-Hady Gepreel M. Niinomi M. (2013). Biocompatibility of Ti-alloys for long-term implantation. J. Mech. Behav. Biomed. Mater. 20, 407–415. 10.1016/j.jmbbm.2012.11.014 Abdolmaleki A. Mallakpour S. Borandeh S. (2014). Tailored functionalization of ZnO nanoparticle via reactive cyclodextrin and its bionanocomposite synthesis. Carbohydr. Polym. 103, 32–37. 10.1016/j.carbpol.2013.12.013 Aijaz A. Karkamkar A. Choi Y. J. Tsumori N. Rönnebro E. Autrey T. (2012). Immobilizing highly catalytically active Pt nanoparticles inside the pores of metal–organic framework: A double solvents approach. J. Am. Chem. Soc. 134, 13926–13929. 10.1021/ja3043905 Al Zoubi W. Yoon D. K. Kim Y. G. Ko Y. G. (2020). Fabrication of organic-inorganic hybrid materials on metal surface for optimizing electrochemical performance. J. Colloid Interface Sci. 573, 31–44. 10.1016/j.jcis.2020.03.117 Albanese A. Chan W. C. (2011). Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS Nano 5, 5478–5489. 10.1021/nn2007496 Almáši M. Zeleňák V. Palotai P. Beňová E. Zeleňáková A. (2018). Metal-organic framework MIL-101(Fe)-NH 2 functionalized with different long-chain polyamines as drug delivery system. Inorg. Chem. Commun. 93, 115–120. 10.1016/j.inoche.2018.05.007 Anfossi L. Di Nardo F. Russo A. Cavalera S. Giovannoli C. Spano G. (2019). Silver and gold nanoparticles as multi-chromatic lateral flow assay probes for the detection of food allergens. Anal. Bioanal. Chem. 411, 1905–1913. 10.1007/s00216-018-1451-6 Ariga K. Jia X. Song J. Hill J. P. Leong D. T. Jia Y. (2020). Nanoarchitectonics beyond self-assembly: Challenges to create bio-like hierarchic organization. Angew. Chem. Int. Ed. 59, 15424–15446. 10.1002/anie.202000802 Arnold P. M. Sasso R. C. Janssen M. E. Fehlings M. G. Heary R. F. Vaccaro A. R. (2016). i-Factor™ bone graft versus autograft in anterior cervical discectomy and fusion: Two-year follow-up of the randomized single-blinded food and drug administration investigational device exemption study. Spine J. 16, S153–S154. 10.1016/j.spinee.2016.07.051 Baekeland L. H. (1909). Sci. Am. 68 (Suppl.), 322. Balazs A. C. Emrick T. Russell T. P. (2006). Nanoparticle polymer composites: Where two small worlds meet. Science 314, 1107–1110. 10.1126/science.1130557 Banerjee S. Das R. K. Maitra U. (2009). Supramolecular gels 'in action'. J. Mater. Chem. 19, 6649–6687. 10.1039/b819218a Basova T. V. Vikulova E. S. Dorovskikh S. I. Hassan A. Morozova N. B. (2021). The use of noble metal coatings and nanoparticles for the modification of medical implant materials. Mater. Des. 204 204, 109672. 10.1016/j.matdes.2021.109672 Belinha J. (2014). Meshless methods in biomechanics. Bone tissue Remodel. anal. Benyettou F. Rezgui R. Ravaux F. Jaber T. Blumer K. Jouiad M. (2015). Synthesis of silver nanoparticles for the dual delivery of doxorubicin and alendronate to cancer cells. J. Mater. Chem. B 3, 7237–7245. 10.1039/c5tb00994d Biggs S. Habgood M. Jameson G. J. Yan Y.-D. (2000). Aggregate structures formed via a bridging flocculation mechanism. Chem. Eng. J. 80, 13–22. 10.1016/s1383-5866(00)00072-1 Bihari P. Vippola M. Schultes S. Praetner M. Khandoga A. G. Reichel C. A. (2008). Optimized dispersion of nanoparticles for biological in vitro and in vivo studies. Part. fibre Toxicol. 5, 14. 10.1186/1743-8977-5-14 Biju V. (2014). Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem. Soc. Rev. 43, 744–764. 10.1039/c3cs60273g Bozo I. Y. Drobyshev A. Y. Redko N. A. Komlev V. S. Isaev A. A. Deev R. V. (2021). Bringing a gene-activated bone substitute into clinical practice: From bench to bedside. Front. Bioeng. Biotechnol. 9, 599300. 10.3389/fbioe.2021.599300 Brasiunas B. Popov A. Ramanavicius A. Ramanaviciene A. (2021). Gold nanoparticle based colorimetric sensing strategy for the determination of reducing sugars. Food Chem. 351, 129238. 10.1016/j.foodchem.2021.129238 Butscher A. Bohner M. Doebelin N. Galea L. Loeffel O. Müller R. (2013). Moisture based three-dimensional printing of calcium phosphate structures for scaffold engineering. Acta Biomater. 9, 5369–5378. 10.1016/j.actbio.2012.10.009 Butscher A. Bohner M. Hofmann S. Gauckler L. Müller R. (2011). Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing. Acta Biomater. 7, 907–920. 10.1016/j.actbio.2010.09.039 Byrappa K. Ohara S. Adschiri T. (2008). Nanoparticles synthesis using supercritical fluid technology - towards biomedical applications. Adv. Drug Deliv. Rev. 60, 299–327. 10.1016/j.addr.2007.09.001 Cai Y. Li H. Du B. Yang M. Li Y. Wu D. (2011). Ultrasensitive electrochemical immunoassay for BRCA1 using BMIM·BF4-coated SBA-15 as labels and functionalized graphene as enhancer. Biomaterials 32, 2117–2123. 10.1016/j.biomaterials.2010.11.058 Cai Y. Wang X. Poh C. K. Tan H. C. Soe M. T. Zhang S. (2014). Accelerated bone growth in vitro by the conjugation of BMP2 peptide with hydroxyapatite on titanium alloy. Colloids and Surfaces B:. Biointerfaces 116, 681–686. 10.1016/j.colsurfb.2013.11.004 Campuzano S. Pedrero M. Nikoleli G. P. Pingarron J. M. Nikolelis D. P. (2017). Hybrid 2D-nanomaterials-based electrochemical immunosensing strategies for clinical biomarkers determination. Biosens. Bioelectron. 89, 269–279. 10.1016/j.bios.2016.01.042 Cao L. Huang Y. Parakhonskiy B. Skirtach A. (2022). Nanoarchitectonics beyond perfect order–not quite perfect but quite useful. Nanoscale 14, 15964–16002. 10.1039/d2nr02537j Casals E. Pfaller T. Duschl A. Oostingh G. J. Puntes V. F. (2011). Hardening of the nanoparticle–protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles. Small 7, 3479–3486. 10.1002/smll.201101511 Chanana M. Rivera_Gil P. Correa-Duarte M. A. Liz-Marzán L. M. Parak W. J. (2013). Physicochemical properties of protein-coated gold nanoparticles in biological fluids and cells before and after proteolytic digestion. Angew. Chem. Int. Ed. 52, 4273–4277. 10.1002/ange.201208019 Chanteau B. Fresnais J. Berret J. F. (2009). Electrosteric enhanced stability of functional sub-10 nm cerium and iron oxide particles in cell culture medium. Langmuir 25, 9064–9070. 10.1021/la900833v Chen Y. G. Li C. X. Zhang Y. Qi Y. D. Liu X. H. Feng J. (2022). Hybrid suture coating for dual-staged control over antibacterial actions to match well wound healing progression. Mater. Horizons 9, 2824–2834. 10.1039/d2mh00591c Chen Y. Lu X. Lamaka S. V. Ju P. Blawert C. Zhang T. (2020). Active protection of Mg alloy by composite PEO coating loaded with corrosion inhibitors. Appl. Surf. Sci. 504, 144462. 10.1016/j.apsusc.2019.144462 Chernozem R. V. Pariy I. Surmeneva M. A. Shvartsman V. V. Plankaert G. Verduijn J. (2022). Cell behavior changes and enzymatic biodegradation of hybrid electrospun poly(3-hydroxybutyrate)-based scaffolds with an enhanced piezoresponse after the addition of reduced graphene oxide. Adv. Healthc. Mater., 2201726. 10.1002/adhm.202201726 Choi Y. Kim S. Choi M. H. Ryoo S. R. Park J. Min D. H. (2014). Highly biocompatible carbon nanodots for simultaneous bioimaging and targeted photodynamic therapy in vitro and in vivo . Adv. Funct. Mater. 24, 5781–5789. 10.1002/adfm.201400961 Christau S. MöLler T. Yenice Z. Genzer J. Von Klitzing R. (2014). Brush/gold nanoparticle hybrids: Effect of grafting density on the particle uptake and distribution within weak polyelectrolyte brushes. Langmuir 30, 13033–13041. 10.1021/la503432x Climent E. Rurack K. (2021). Combining electrochemiluminescence detection with aptamer-gated indicator releasing mesoporous nanoparticles enables ppt sensitivity for strip-based rapid tests. Angew. Chemie-International Ed. 60, 26287–26297. 10.1002/anie.202110744 Cui H. Shao Z.-S. Song Z. Wang Y.-B. Wang H.-S. (2020). Development of gold nanoclusters: From preparation to applications in the field of biomedicine. J. Mater. Chem. C 8, 14312–14333. 10.1039/d0tc03443f Cui Q. He F. Li L. Möhwald H. (2014). Controllable metal-enhanced fluorescence in organized films and colloidal system. Adv. Colloid Interface Sci. 207, 164–177. 10.1016/j.cis.2013.10.011 Cui W. Wang A. Zhao J. Li J. (2016). Biomacromolecules based core/shell architecture toward biomedical applications. Adv. Colloid Interface Sci. 237, 43–51. 10.1016/j.cis.2016.10.001 Dai X. Zhao X. Liu Y. Chen B. Ding X. Zhao N. (2021). Controlled synthesis and surface engineering of janus chitosan-gold nanoparticles for photoacoustic imaging-guided synergistic gene/photothermal therapy. Small 17, 2006004. 10.1002/smll.202006004 De Gennes P. G. (1987). Polymers at an interface; a simplified view. Adv. Colloid Interface Sci. 27, 189–209. 10.1016/0001-8686(87)85003-0 Del Pino P. Pelaz B. Zhang Q. Maffre P. Nienhaus G. U. Parak W. J. (2014). Protein corona formation around nanoparticles–from the past to the future. Mater. Horizons 1, 301–313. 10.1039/c3mh00106g Deng M. Wang L. Hoche D. Lamaka S. V. Wang C. Snihirova D. (2021). Approaching "stainless magnesium" by Ca micro-alloying. Mater. horizons 8, 589–596. 10.1039/d0mh01380c Digiovanni C. W. Lin S. S. Baumhauer J. F. Daniels T. Younger A. Glazebrook M. (2013). Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP): An alternative to autogenous bone graft. J. Bone Jt. Surg. Am. Volume 95, 1184–1192. 10.2106/jbjs.k.01422 Digiovanni C. W. Lin S. S. Daniels T. R. Glazebrook M. Evangelista P. Donahue R. (2016). The importance of sufficient graft material in achieving foot or ankle fusion. J. Bone Jt. Surg. Am. Volume 98, 1260–1267. 10.2106/jbjs.15.00879 Ding C. Zhu A. Tian Y. (2014). Functional surface engineering of C-dots for fluorescent biosensing and in vivo bioimaging. Accounts Chem. Res. 47, 20–30. 10.1021/ar400023s Duan X. P. Chan C. Lin W. B. (2019). Nanoparticle-Mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angew. Chemie-International Ed. 58, 670–680. 10.1002/anie.201804882 Dutta S. Strack G. Kurup P. (2019). Gold nanostar electrodes for heavy metal detection. Sensors and Actuators B:. Chemical 281, 383–391. 10.1016/j.snb.2018.10.111 Edwards S. Williams D. (2004). Double layers and interparticle forces in colloid science and biology: Analytic results for the effect of ionic dispersion forces. Phys. Rev. Lett. 92, 248303. 10.1103/physrevlett.92.248303 Elbakry A. Zaky A. Liebl R. Rachel R. Goepferich A. Breunig M. (2009). Layer-by-Layer assembled gold nanoparticles for siRNA delivery. Nano Lett. 9, 2059–2064. 10.1021/nl9003865 Espinosa A. Reguera J. Curcio A. Munoz-Noval A. Kuttner C. Van De Walle A. (2020). Janus magnetic-plasmonic nanoparticles for magnetically guided and thermally activated cancer therapy. Small (Weinheim der Bergstrasse, Ger. 16, e1904960. 10.1002/smll.201904960 Fan H. Wang L. Zhao K. Li N. Shi Z. Ge Z. (2010). Fabrication, mechanical properties, and biocompatibility of graphene-reinforced chitosan composites. Biomacromolecules 11, 2345–2351. 10.1021/bm100470q Feng H. Qian Z. (2018). Functional carbon quantum dots: A versatile platform for chemosensing and biosensing. Chemical record (New York, N.Y.) . Chem. Rec. 18, 491–505. 10.1002/tcr.201700055 Feng L. Li W. Bao J. Zheng Y. Li Y. Ma Y. (2019). Synthesis and luminescence properties of core-shell-shell composites: SiO2@PMDA-Si-Tb@SiO2 and SiO2@PMDA-Si-Tb-phen@SiO2. Nanomaterials (basel, Switzerland) 9. Feoktistova N. A. Balabushevich N. G. Skirtach A. G. Volodkin D. Vikulina A. S. (2020). Inter-protein interactions govern protein loading into porous vaterite CaCO3 crystals. Phys. Chem. Chem. Phys. PCCP 22, 9713–9722. 10.1039/d0cp00404a Foldbjerg R. Jiang X. Miclăuş T. Chen C. Autrup H. Beer C. (2015). Silver nanoparticles – wolves in sheep's clothing? Toxicol. Res. 4, 563–575. 10.1039/c4tx00110a Fraire J. C. Stremersch S. Bouckaert D. Monteyne T. De Beer T. Wuytens P. (2019). Improved label-free identification of individual exosome-like vesicles with Au@Ag nanoparticles as SERS substrate. ACS Appl. Mater. interfaces 11, 39424–39435. 10.1021/acsami.9b11473 Fu Q. Xiao S. Tang X. Chen Y. Hu T. (2019). Amphiphilic fullerenes employed to improve the quality of perovskite films and the stability of perovskite solar cells. ACS Appl. Mater. Interfaces 11, 24782–24788. 10.1021/acsami.9b07149 Gaharwar A. K. Cross L. M. Peak C. W. Gold K. Carrow J. K. Brokesh A. (2019). 2D nanoclay for biomedical applications: Regenerative medicine, therapeutic delivery, and additive manufacturing. Adv. Mater. 31, 1900332. 10.1002/adma.201900332 Gao C. Lin Z. Wu Z. Lin X. He Q. (2016). Stem-cell-membrane camouflaging on near-infrared photoactivated upconversion nanoarchitectures for in vivo remote-controlled photodynamic therapy. ACS Appl. Mater. interfaces 8, 34252–34260. 10.1021/acsami.6b12865 Gaponik N. Rogach A. L. (2010). Thiol-capped CdTe nanocrystals: Progress and perspectives of the related research fields. Phys. Chem. Chem. Phys. 12, 8685–8693. 10.1039/c000916d Garg S. Serruys P. W. (2010). Coronary stents: Current status. J. Am. Coll. Cardiol. 56, S1–S42. 10.1016/j.jacc.2010.06.007 Gitipour A. Thiel S. W. Scheckel K. G. Tolaymat T. (2016). Anaerobic toxicity of cationic silver nanoparticles. Sci. Total Environ. 557-558, 363–368. 10.1016/j.scitotenv.2016.02.190 Glazebrook M. Younger A. Wing K. Lalonde K.-A. (2013). A prospective pilot study of B2A-coated ceramic granules (Amplex) compared to autograft for ankle and hindfoot arthrodesis. Foot Ankle Int. 34, 1055–1063. 10.1177/1071100713481459 Go Y. K. Leal C. (2021). Polymer-lipid hybrid materials. Chem. Rev. 121, 13996–14030. 10.1021/acs.chemrev.1c00755 Goodyear C. (1856). Dinglers Polytech. J. 139, 376. Graf C. Gao Q. Schütz I. Noufele C. N. Ruan W. Posselt U. (2012). Surface functionalization of silica nanoparticles supports colloidal stability in physiological media and facilitates internalization in cells. Langmuir 28, 7598–7613. 10.1021/la204913t Gu Y. Yu L. Mou J. Wu D. Xu M. Zhou P. (2020). Research strategies to develop environmentally friendly marine antifouling coatings. Mar. Drugs 18 18, 371. 10.3390/md18070371 Guner H. Ozgur E. Kokturk G. Celik M. Esen E. Topal A. E. (2017). A smartphone based surface plasmon resonance imaging (SPRi) platform for on-site biodetection. Sensors and actuators B:. Chemical 239, 571–577. 10.1016/j.snb.2016.08.061 Guo X. Li X. Chan L. Huang W. Chen T. (2021). Edible CaCO3 nanoparticles stabilized Pickering emulsion as calcium-fortified formulation. J. nanobiotechnology 19, 67–16. 10.1186/s12951-021-00807-6 Guo Y. Jia H. R. Zhang X. Zhang X. Sun Q. Wang S. Z. (2020). A glucose/oxygen-exhausting nanoreactor for starvation-and hypoxia-activated sustainable and cascade chemo-chemodynamic therapy. Small 16, 2000897. 10.1002/smll.202000897 Gupta B. Poudel B. K. Ruttala H. B. Regmi S. Pathak S. Gautam M. (2018). Hyaluronic acid-capped compact silica-supported mesoporous titania nanoparticles for ligand-directed delivery of doxorubicin. Acta Biomater. 80, 364–377. 10.1016/j.actbio.2018.09.006 Han L. Jiang Y. Lv C. Gan D. Wang K. Ge X. (2019). Mussel-inspired hybrid coating functionalized porous hydroxyapatite scaffolds for bone tissue regeneration. Colloids and Surfaces B:. Biointerfaces 179, 470–478. 10.1016/j.colsurfb.2019.04.024 Haskell A. K. Sulman A. M. Golikova E. P. Stein B. D. Pink M. Morgan D. G. (2020). Glucose oxidase immobilized on magnetic zirconia: Controlling catalytic performance and stability. ACS omega 5, 12329–12338. 10.1021/acsomega.0c01067 Heuer-Jungemann A. Feliu N. Bakaimi I. Hamaly M. Alkilany A. Chakraborty I. (2019). The role of ligands in the chemical synthesis and applications of inorganic nanoparticles. Chem. Rev. 119, 4819–4880. 10.1021/acs.chemrev.8b00733 Hirt N. Body-Malapel M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: A review of the literature. Part. Fibre Toxicol. 17, 57. 10.1186/s12989-020-00387-7 Ho-Shui-Ling A. Bolander J. Rustom L. E. Johnson A. W. Luyten F. P. Picart C. (2018). Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials 180, 143–162. 10.1016/j.biomaterials.2018.07.017 Hou J. Dong G. Luu B. Sengpiel R. G. Ye Y. Wessling M. (2014). Hybrid membrane with TiO2 based bio-catalytic nanoparticle suspension system for the degradation of bisphenol-A. Bioresour. Technol. 169, 475–483. 10.1016/j.biortech.2014.07.031 Hua Z. Yu T. Liu D. Xianyu Y. (2021). Recent advances in gold nanoparticles-based biosensors for food safety detection. Biosens. Bioelectron. 179, 113076. 10.1016/j.bios.2021.113076 Huang X. Tan C. L. Yin Z. Y. Zhang H. (2014a). 25th anniversary article: Hybrid nanostructures based on two-dimensional nanomaterials. Adv. Mater. 26, 2185–2204. 10.1002/adma.201304964 Huang X. Tepylo N. Pommier-Budinger V. Budinger M. Bonaccurso E. Villedieu P. (2019). A survey of icephobic coatings and their potential use in a hybrid coating/active ice protection system for aerospace applications. Prog. Aerosp. Sci. 105, 74–97. 10.1016/j.paerosci.2019.01.002 Huang Y. Cao L. Parakhonskiy B. V. Skirtach A. G. (2022). Hard, soft, and hard-and-soft drug delivery carriers based on CaCO3 and alginate biomaterials: Synthesis, properties, pharmaceutical applications. Pharmaceutics 14, 909. 10.3390/pharmaceutics14050909 Huang Y. Ng H. C. Ng X. W. Subbu V. (2014b). Drug-eluting biostable and erodible stents. J. Control. release official J. Control. Release Soc. 193, 188–201. 10.1016/j.jconrel.2014.05.011 Huang Y. Zhou J. Feng H. Zheng J. Ma H.-M. Liu W. (2016). A dual-channel fluorescent chemosensor for discriminative detection of glutathione based on functionalized carbon quantum dots. Biosens. Bioelectron. 86, 748–755. 10.1016/j.bios.2016.07.081 Ikeda A. (2013). Water-soluble fullerenes using solubilizing agents, and their applications. J. Inclusion Phenom. Macrocycl. Chem. 77, 49–65. 10.1007/s10847-013-0319-9 Iqbal J. Gunn J. Serruys P. W. (2013). Coronary stents: Historical development, current status and future directions. Br. Med. Bull. 106, 193–211. 10.1093/bmb/ldt009 Ji S. Wang Q. Xu Q. Wu M. Shi W. (2020a). Electrospun organic/inorganic hybrid nanofibers as low-cytotoxicity and recyclable photocatalysts. Appl. Surf. Sci. 532 532, 147430. 10.1016/j.apsusc.2020.147430 Ji X. Yuan X. Ma L. Bi B. Zhu H. Lei Z. (2020b). Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(ε-caprolactone)/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation. Theranostics 10, 725–740. 10.7150/thno.39167 Jiang G. Erdem O. Hübner R. Georgi M. Wei W. Fan X. (2021). Mechanosynthesis of polymer-stabilized lead bromide perovskites: Insight into the formation and phase conversion of nanoparticles. Nano Res. 14, 1078–1086. 10.1007/s12274-020-3152-7 Jun Y. W. Seo J. W. Cheon A. (2008). Nanoscaling laws of magnetic nanoparticles and their applicabilities in biomedical sciences. Accounts Chem. Res. 41, 179–189. 10.1021/ar700121f Kang H. Buchman J. T. Rodriguez R. S. Ring H. L. He J. Bantz K. C. (2019). Stabilization of silver and gold nanoparticles: Preservation and improvement of plasmonic functionalities. Chem. Rev. 119, 664–699. 10.1021/acs.chemrev.8b00341 Karthick V. Shrestha L. K. Kumar V. G. Pranjali P. Kumar D. Pal A. (2022). Nanoarchitectonics horizons: Materials for life sciences. Nanoscale 14, 10630–10647. 10.1039/d2nr02293a Kaufmann A. Hampel S. Rieger C. Kunhardt D. Schendel D. Füssel S. (2017). Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes. J. nanobiotechnology 15, 53. 10.1186/s12951-017-0288-z Kaushik M. Moores A. (2016). Review: Nanocelluloses as versatile supports for metal nanoparticles and their applications in catalysis. Green Chem. 18, 622–637. 10.1039/c5gc02500a Kiadeh S. Z. H. Ghaee A. Farokhi M. Nourmohammadi J. Bahi A. Ko F. K. (2021). S., Ghaee, A., Farokhi, M., Nourmohammadi, J., Bahi, A., and Ko, F.KElectrospun pectin/modified copper-based metal-organic framework (MOF) nanofibers as a drug delivery system. Int. J. Biol. Macromol. 173, 351–365. 10.1016/j.ijbiomac.2021.01.058 Kickelbick G. (2003). Concepts for the incorporation of inorganic building blocks into organic polymers on a nanoscale. Prog. Polym. Sci. 28, 83–114. 10.1016/s0079-6700(02)00019-9 Kim D.-Y. Kim M. Shinde S. Sung J.-S. Ghodake G. (2017). Cytotoxicity and antibacterial assessment of gallic acid capped gold nanoparticles. Colloids and Surfaces B:. Biointerfaces 149, 162–167. 10.1016/j.colsurfb.2016.10.017 King B. M. Fiegel J. (2022). Zwitterionic polymer coatings enhance gold nanoparticle stability and uptake in various biological environments. AAPS J. 24, 18. 10.1208/s12248-021-00652-3 Kopecek J. (2009). Hydrogels: From soft contact lenses and implants to self-assembled nanomaterials. J. Polym. Sci. Part a-Polymer Chem. 47, 5929–5946. 10.1002/pola.23607 Kozlova A. A. German S. V. Atkin V. S. Zyev V. V. Astle M. A. Bratashov D. N. (2020). Magnetic composite submicron carriers with structure-dependent MRI contrast. Inorganics 8, 11. 10.3390/inorganics8020011 Lavrador P. Esteves M. R. Gaspar V. M. Mano J. F. (2021). Stimuli-responsive nanocomposite hydrogels for biomedical applications. Adv. Funct. Mater. 31, 2005941. 10.1002/adfm.202005941 Lee H. (2021). Molecular modeling of protein corona formation and its interactions with nanoparticles and cell membranes for nanomedicine applications. Pharm. 13 13, 637. 10.3390/pharmaceutics13050637 Lee H. Dellatore S. M. Miller W. M. Messersmith P. B. (2007). Mussel-inspired surface chemistry for multifunctional coatings. Sci. (New York, N.Y.) 318, 426–430. 10.1126/science.1147241 Lee J. W. Choi S.-R. Heo J. H. (2021). Simultaneous stabilization and functionalization of gold nanoparticles via biomolecule conjugation: Progress and perspectives. ACS Appl. Mater. Interfaces 13, 42311–42328. 10.1021/acsami.1c10436 Lee M.-Y. Park S.-J. Park K. Kim K. S. Lee H. Hahn S. K. (2011). Target-specific gene silencing of layer-by-layer assembled gold-cysteamine/siRNA/PEI/HA nanocomplex. ACS Nano 5, 6138–6147. 10.1021/nn2017793 Lengert E. Parakhonskiy B. Khalenkow D. Zečić A. Vangheel M. Moreno J. M. M. (2018). Laser-induced remote release in vivo in C. elegans from novel silver nanoparticles-alginate hydrogel shells. Nanoscale 10, 17249–17256. 10.1039/c8nr00893k Lengert E. Saveleva M. Abalymov A. Atkin V. Wuytens P. C. Kamyshinsky R. (2017). Silver alginate hydrogel micro- and nanocontainers for theranostics: Synthesis, encapsulation, remote release, and detection. ACS Appl. Mater. interfaces 9, 21949–21958. 10.1021/acsami.7b08147 Leroux F. Rabu P. Sommerdijk N. A. Taubert A. (2015). Two-Dimensional hybrid materials: Transferring technology from biology to society. Eur. J. Inorg. Chem. 2015, 1089–1095. 10.1002/ejic.201500153 Levy L. Gurov A. Radian A. (2020). The effect of gallic acid interactions with iron-coated clay on surface redox reactivity. Water Res. 184, 116190. 10.1016/j.watres.2020.116190 Lewinski N. Colvin V. Drezek R. (2008). Cytotoxicity of nanoparticles. Small (Weinheim Der Bergstrasse, Ger. 4, 26–49. 10.1002/smll.200700595 Li B. K. Cui Y. H. Wang X. Y. Tang R. K. (2021a). Novel nanomaterial-organism hybrids with biomedical potential. Wiley Interdiscip. Reviews-Nanomedicine Nanobiotechnology 13 13, e1706. 10.1002/wnan.1706 Li C. Zhang Y. Li Z. Mei E. Lin J. Li F. (2018a). Theranostics: Light-Responsive biodegradable nanorattles for cancer theranostics (adv. Mater. 8/2018). Adv. Mater. 30, 1870049. 10.1002/adma.201870049 Li C. Zhao Z. H. Luo Y. F. Ning T. T. Liu P. X. Chen Q. J. (2021b). Macrophage-disguised manganese dioxide nanoparticles for neuroprotection by reducing oxidative stress and modulating inflammatory microenvironment in acute ischemic stroke. Adv. Sci. 8 8, 2101526. 10.1002/advs.202101526 Li J. Feng X. Fei J. Cai P. Huang J. Li J. (2016). Integrating photosystem II into a porous TiO2 nanotube network toward highly efficient photo-bioelectrochemical cells. J. Mater. Chem. A 4, 12197–12204. 10.1039/c6ta04964h Li J. Khalenkow D. Volodkin D. Lapanje A. Skirtach A. G. Parakhonskiy B. V. (2022a). Surface enhanced Raman scattering (SERS)-active bacterial detection by Layer-by-Layer (LbL) assembly all-nanoparticle microcapsules.” in Colloids and surfaces A: Physicochemical and engineering aspects. Li J. Parakhonskiy B. V. Skirtach A. G. (2022b). A decade of developing applications exploiting the properties of polyelectrolyte multilayer capsules. Chem. Commun. Camb. Engl. 10.1039/d2cc04806j Li Q. F. Zeng L. X. Wang J. C. Tang D. P. Liu B. Q. Chen G. N. (2011). Magnetic mesoporous organic-inorganic NiCo2O4 hybrid nanomaterials for electrochemical immunosensors. Acs Appl. Mater. Interfaces 3, 1366–1373. 10.1021/am200228k Li X. Luo W. Ng T. W. Leung P. C. Zhang C. Leung K. C.-F. (2017). Nanoparticle-encapsulated baicalein markedly modulates pro-inflammatory response in gingival epithelial cells. Nanoscale 9, 12897–12907. 10.1039/c7nr02546g Li X. Wei J. Li Q. Zheng S. Xu Y. Du P. (2018b). Nitrogen-doped cobalt oxide nanostructures derived from cobalt–alanine complexes for high-performance oxygen evolution reactions. Adv. Funct. Mater. 28, 1800886. 10.1002/adfm.201800886 Li Y. He L. Huang C. Z. Li Y. F. (2019). Silver-based metal-organic gels as novel coreactant for enhancing electrochemiluminescence and its biosensing potential. Biosens. Bioelectron. 134, 29–35. 10.1016/j.bios.2019.03.058 Li Y. Yang W. Li X. Zhang X. Wang C. Meng X. (2015). Improving osteointegration and osteogenesis of three-dimensional porous Ti6Al4V scaffolds by polydopamine-assisted biomimetic hydroxyapatite coating. ACS Appl. Mater. interfaces 7, 5715–5724. 10.1021/acsami.5b00331 Lim S. Y. Shen W. Gao Z. (2015). Carbon quantum dots and their applications. Chem. Soc. Rev. 44, 362–381. 10.1039/c4cs00269e Lin L. S. Yang X. Y. Niu G. Song J. B. Yang H. H. Chen X. Y. (2016). Dual-enhanced photothermal conversion properties of reduced graphene oxide-coated gold superparticles for light-triggered acoustic and thermal theranostics. Nanoscale 8, 2116–2122. 10.1039/c5nr07552a Lisuzzo L. Cavallaro G. Milioto S. Lazzara G. (2019). Layered composite based on halloysite and natural polymers: A carrier for the pH controlled release of drugs. New J. Chem. 43, 10887–10893. 10.1039/c9nj02565k Liu D. Wang Z. Jiang X. (2011). Gold nanoparticles for the colorimetric and fluorescent detection of ions and small organic molecules. Nanoscale 3, 1421–1433. 10.1039/c0nr00887g Liu J. L. Shi W. X. Wang X. (2019). Cluster-nuclei coassembled into two-dimensional hybrid CuO-pma sub-1 nm nanosheets. J. Am. Chem. Soc. 141, 18754–18758. 10.1021/jacs.9b08818 Liu M. Qiu X. Q. Hashirnoto K. Miyauchi M. (2014). Cu(II) nanocluster-grafted, Nb-doped TiO2 as an efficient visible-light-sensitive photocatalyst based on energy-level matching between surface and bulk states. J. Mater. Chem. A 2, 13571–13579. 10.1039/c4ta02211d Liu N. Tang M. Ding J. (2020a). The interaction between nanoparticles-protein corona complex and cells and its toxic effect on cells. Chemosphere 245, 125624. 10.1016/j.chemosphere.2019.125624 Liu R. Jiang L. Yu Z. Jing X. Liang X. Wang D. (2021). MXene (Ti3C2Tx)-Ag nanocomplex as efficient and quantitative SERS biosensor platform by in-situ PDDA electrostatic self-assembly synthesis strategy. Sensors and Actuators B:. Chemical 333, 129581. 10.1016/j.snb.2021.129581 Liu S. Chen X. Bao L. Liu T. Yuan P. Yang X. (2020b). Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles. Nat. Biomed. Eng. 4, 1063–1075. 10.1038/s41551-020-00637-1 Lutich A. A. Jiang G. Susha A. S. Rogach A. L. Stefani F. D. Feldmann J. (2009). Energy transfer versus charge separation in type-ii hybrid organic− inorganic nanocomposites. Nano Lett. 9, 2636–2640. 10.1021/nl900978a Lv H. Cui S. Yang Q. Song X. Wang D. Hu J. (2021). AgNPs-incorporated nanofiber mats: Relationship between AgNPs size/content, silver release, cytotoxicity, and antibacterial activity. Mater. Sci. Eng. C 118, 111331. 10.1016/j.msec.2020.111331 Lvov Y. M. Shchukin D. G. Mohwald H. Price R. R. (2008). Halloysite clay nanotubes for controlled release of protective agents. ACS Nano 2, 814–820. 10.1021/nn800259q Mahmood A. Guo W. H. Tabassum H. Zou R. Q. (2016). Metal-Organic framework-based nanomaterials for electrocatalysis. Adv. Energy Mater. 6 6, 1600423. 10.1002/aenm.201600423 Majumder J. Minko T. (2021). Targeted nanotherapeutics for respiratory diseases: Cancer, fibrosis, and coronavirus. Adv. Ther. 4, 2000203. Mann S. (2009). Self-assembly and transformation of hybrid nano-objects and nanostructures under equilibrium and non-equilibrium conditions. Nat. Mater. 8, 781–792. 10.1038/nmat2496 Martinelli A. Nitti A. Giannotta G. Po R. Pasini D. (2022). 3D printing of conductive organic polymers: Challenges and opportunities towards dynamic and electrically responsive materials. Mater. Today Chem. 26, 101135. 10.1016/j.mtchem.2022.101135 Mcmahon A. Chen W. Li F. (2020). Old wine in new bottles: Advanced drug delivery systems for disulfiram-based cancer therapy. J. Control. release official J. Control. Release Soc. 319, 352–359. 10.1016/j.jconrel.2020.01.001 Mehdikhani-Nahrkhalaji M. Fathi M. H. Mortazavi V. Mousavi S. B. Akhavan A. Haghighat A. (2015). Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation. Dent. Res. J. 12, 89–99. 10.4103/1735-3327.150342 Melnikau D. Esteban R. Savateeva D. Sánchez-Iglesias A. Grzelczak M. Schmidt M. K. (2016). Rabi splitting in photoluminescence spectra of hybrid systems of gold nanorods and J-aggregates. J. Phys. Chem. Lett. 7, 354–362. 10.1021/acs.jpclett.5b02512 Melnikau D. Hendel T. Linkov P. A. Samokhvalov P. S. Nabiev I. R. Rakovich Y. P. (2018). Energy transfer between single semiconductor quantum dots and organic dye molecules. Zeitschrift Fur Physikalische Chemie-International J. Res. Phys. Chem. Chem. Phys. 232, 1513–1526. 10.1515/zpch-2018-1144 Mirkin C. A. Letsinger R. L. Mucic R. C. Storhoff J. J. (1996). A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609. 10.1038/382607a0 Miyazawa A. Ako J. Hongo Y. Hur S.-H. Tsujino I. Courtney B. K. (2008). Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent: Intravascular ultrasound results from ENDEAVOR III. Am. Heart J. 155, 108–113. 10.1016/j.ahj.2007.08.008 Moglia I. Santiago M. Guerrero S. Soler M. Olivera-Nappa A. Kogan M. J. (2021). Enhanced cellular uptake of H-chain human ferritin containing gold nanoparticles. Pharm. 13 13, 1966. 10.3390/pharmaceutics13111966 Moore T. L. Rodriguez-Lorenzo L. Hirsch V. Balog S. Urban D. Jud C. (2015). Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem. Soc. Rev. 44, 6287–6305. 10.1039/c4cs00487f Moreels I. Fritzinger B. Martins J. C. Hens Z. (2008). Surface chemistry of colloidal PbSe nanocrystals. J. Am. Chem. Soc. 130, 15081–15086. 10.1021/ja803994m Mosquera J. García I. Henriksen-Lacey M. González-Rubio G. Liz-Marzán L. M. (2018). Reducing protein corona formation and enhancing colloidal stability of gold nanoparticles by capping with silica monolayers. Chem. Mater. 31, 57–61. 10.1021/acs.chemmater.8b04647 Moustafa H. Morsy M. Ateia M. A. Abdel-Haleem F. M. (2021). Ultrafast response humidity sensors based on polyvinyl chloride/graphene oxide nanocomposites for intelligent food packaging. Sensors Actuators a-Physical 331 331, 112918. 10.1016/j.sna.2021.112918 Mu W. Chu Q. Liu Y. Zhang N. (2020). A review on nano-based drug delivery system for cancer chemoimmunotherapy. Nano-Micro Lett. 12, 142–165. 10.1007/s40820-020-00482-6 Muderrisoglu C. Saveleva M. Abalymov A. Van Der Meeren L. Ivanova A. Atkin V. (2018). Nanostructured biointerfaces based on bioceramic calcium carbonate/hydrogel coatings on titanium with an active enzyme for stimulating osteoblasts growth. Adv. Mater. Interfaces 5 5, 1800452. 10.1002/admi.201800452 Mulvaney P. Giersig M. Henglein A. (1992). Surface chemistry of colloidal gold: Deposition of lead and accompanying optical effects. J. Phys. Chem. 96, 10419–10424. 10.1021/j100204a056 Murugappan G. Sreeram K. J. (2021). Nano-biocatalyst: Bi-Functionalization of protease and amylase on copper oxide nanoparticles. Colloids surfaces. B, Biointerfaces 197, 111386. 10.1016/j.colsurfb.2020.111386 Nam Y. T. Choi J. Kang K. M. Kim D. W. Jung H.-T. (2016). Enhanced stability of laminated graphene oxide membranes for nanofiltration via interstitial amide bonding. ACS Appl. Mater. Interfaces 8, 27376–27382. 10.1021/acsami.6b09912 Nekoueian K. Amiri M. Sillanpää M. Marken F. Boukherroub R. Szunerits S. (2019). Carbon-based quantum particles: An electroanalytical and biomedical perspective. Chem. Soc. Rev. 48, 4281–4316. 10.1039/c8cs00445e Ni K. Y. Luo T. K. Nash G. T. Lin W. B. (2020). Nanoscale metal-organic frameworks for cancer immunotherapy. Accounts Chem. Res. 53, 1739–1748. 10.1021/acs.accounts.0c00313 Nie S. (2010). Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine Lond. Engl. 5, 523–528. 10.2217/nnm.10.23 Niinomi M. Nakai M. Hieda J. (2012). Development of new metallic alloys for biomedical applications. Acta biomater. 8, 3888–3903. 10.1016/j.actbio.2012.06.037 Nitti A. Carfora R. Assanelli G. Notari M. Pasini D. (2022). Single-Chain polymer nanoparticles for addressing morphologies and functions at the nanoscale: A review. ACS Appl. Nano Mater. 5, 13985–13997. 10.1021/acsanm.2c02313 Nugroho F. a. A. Eklund R. Nilsson S. Langhammer C. (2018). A fiber-optic nanoplasmonic hydrogen sensor via pattern-transfer of nanofabricated PdAu alloy nanostructures. Nanoscale 10, 20533–20539. 10.1039/c8nr03751e Oladimeji O. Akinyelu J. Daniels A. Singh M. (2021). Modified gold nanoparticles for efficient delivery of betulinic acid to cancer cell mitochondria. Int. J. Mol. Sci. 22, 5072. 10.3390/ijms22105072 Orlovskii V. Komlev V. Barinov S. (2002). Hydroxyapatite and hydroxyapatite-based ceramics. Inorg. Mater. 38, 973–984. 10.1023/a:1020585800572 Pal S. (2014). Design of artificial human joints & organs. Springer. Panáček A. Kvítek L. Smékalová M. Večeřová R. Kolář M. Röderová M. (2018). Bacterial resistance to silver nanoparticles and how to overcome it. Nat. Nanotechnol. 13, 65–71. 10.1038/s41565-017-0013-y Papafaklis M. I. Chatzizisis Y. S. Naka K. K. Giannoglou G. D. Michalis L. K. (2012). Drug-eluting stent restenosis: Effect of drug type, release kinetics, hemodynamics and coating strategy. Pharmacol. Ther. 134, 43–53. 10.1016/j.pharmthera.2011.12.006 Parakhonskiy B. Bedard M. Bukreeva T. Sukhorukov G. Mohwald H. Skirtach A. (2010). Nanoparticles on polyelectrolytes at low concentration: Controlling concentration and size. J. Phys. Chem. C 114, 1996–2002. 10.1021/jp904564v Parakhonskiy B. V. Foss C. Carletti E. Fedel M. Haase A. Motta A. (2013). Tailored intracellular delivery via a crystal phase transition in 400 nm vaterite particles. Biomaterials Sci. 1, 1273–1281. 10.1039/c3bm60141b Parakhonskiy B. V. Haase A. Antolini R. (2012a). Sub-micrometer vaterite containers: Synthesis, substance loading, and release. Angewandte Chemie Int. ed. Engl. 51, 1221–1223. 10.1002/ange.201104316 Parakhonskiy B. V. Haase A. Antolini R. (2012b). Sub-micrometer vaterite containers: Synthesis, substance loading, and release. Angew. Chem. 124, 1221–1223. 10.1002/ange.201104316 Parakhonskiy B. V. Shilyagina N. Y. Gusliakova О. I. Volovetskiy A. B. Kostyuk A. B. Balalaeva I. V. (2021). A method of drug delivery to tumors based on rapidly biodegradable drug-loaded containers. Appl. Mater. Today 25 25, 101199. 10.1016/j.apmt.2021.101199 Parakhonskiy B. V. Svenskaya Y. I. Yashchenok Acapital Em C. Fattah H. A. Inozemtseva O. A. Tessarolo F. (2014). Size controlled hydroxyapatite and calcium carbonate particles: Synthesis and their application as templates for SERS platform. Colloids surfaces. B, Biointerfaces 118, 243–248. 10.1016/j.colsurfb.2014.03.053 Patungwasa W. Hodak J. H. (2008). pH tunable morphology of the gold nanoparticles produced by citrate reduction. Mater. Chem. Phys. 108, 45–54. 10.1016/j.matchemphys.2007.09.001 Peer D. Karp J. M. Hong S. Farokhzad O. C. Margalit R. Langer R. (2020). Nanocarriers as an emerging platform for cancer therapy. Nano-Enabled Med. Appl., 61–91. 10.1201/9780429399039-2 Petry R. Saboia V. M. Franqui L. S. Holanda C. D. A. Garcia T. R. R. De Farias M. A. (2019). On the formation of protein corona on colloidal nanoparticles stabilized by depletant polymers. Mater. Sci. Eng. C, Mater. Biol. Appl. 105, 110080. 10.1016/j.msec.2019.110080 Pham M. D. Epperla C. P. Hsieh C.-L. Chang W. Chang H.-C. (2017). Glycosaminoglycans-specific cell targeting and imaging using fluorescent nanodiamonds coated with viral envelope proteins. Anal. Chem. 89, 6527–6534. 10.1021/acs.analchem.7b00627 Prabakaran S. Rajan M. Geng Z. Liu Y. (2021). Fabrication of substituted hydroxyapatite-starch-clay bio-composite coated titanium implant for new bone formation. Carbohydr. Polym. 271, 118432. 10.1016/j.carbpol.2021.118432 Qin C. Fei J. Wang A. Yang Y. Li J. (2015). Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapycore@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy. Nanoscale 7, 20197–20210. 10.1039/c5nr06501a Rabie H. Zhang Y. Pasquale N. Lagos M. J. Batson P. E. Lee K. B. (2019). NIR biosensing of neurotransmitters in stem cell-derived neural interface using advanced core–shell upconversion nanoparticles. Adv. Mater. 31, 1806991. 10.1002/adma.201806991 Radziuk D. Shchukin D. G. Skirtach A. Möhwald H. Sukhorukov G. (2007). Synthesis of silver nanoparticles for remote opening of polyelectrolyte microcapsules. Langmuir 23, 4612–4617. 10.1021/la063420w Rahman M. M. Balu R. Abraham A. Dutta N. K. Choudhury N. R. (2021). Engineering a bioactive hybrid coating for in vitro corrosion control of magnesium and its alloy. ACS applied bio materials 4, 5542–5555. Rapetto C. Leoncini M. (2017). Magmaris: A new generation metallic sirolimus-eluting fully bioresorbable scaffold: Present status and future perspectives. J. Thorac. Dis. 9, S903–S913. 10.21037/jtd.2017.06.34 Rigoletto M. Calza P. Gaggero E. Laurenti E. (2022). Hybrid materials for the removal of emerging pollutants in water: Classification, synthesis, and properties. Chem. Eng. J. Adv. 10 10, 100252. 10.1016/j.ceja.2022.100252 Roberts T. C. Langer R. Wood M. J. A. (2020). Advances in oligonucleotide drug delivery. Nat. Rev. Drug Discov. 19, 673–694. 10.1038/s41573-020-0075-7 Ruiz-Aguilar C. Aguilar-Reyes E. Flores-Martínez M. León-Patiño C. Nuñéz-Anita R. (2017). Synthesis and characterisation of β-TCP/bioglass/zirconia scaffolds. Adv. Appl. Ceram. 116, 452–461. 10.1080/17436753.2017.1356043 Ruiz-Hitzky E. Ariga K. Lvov Y. M. E. (2008). Bio-inorganic hybrid nanomaterials: Strategies, synthesis, characterization and applications. Wiley-VCH Verlag GmbH Co. KGaA, Weinheim, Ger. Saba N. Jawaid M. Alothman O. Y. Paridah M. T. (2016). A review on dynamic mechanical properties of natural fibre reinforced polymer composites. Constr. Build. Mater. 106, 149–159. 10.1016/j.conbuildmat.2015.12.075 Safi M. Courtois J. Seigneuret M. Conjeaud H. Berret J. F. (2011). The effects of aggregation and protein corona on the cellular internalization of iron oxide nanoparticles. Biomaterials 32, 9353–9363. 10.1016/j.biomaterials.2011.08.048 Sanchez C. Soler-Illia G. J. a. A. (2006). Hybrid materials. Encyclop. Chem. Proc. Sanchez C. Belleville P. Popall M. Nicole L. (2011). Applications of advanced hybrid organic-inorganic nanomaterials: From laboratory to market. Chem. Soc. Rev. 40, 696–753. 10.1039/c0cs00136h Sanchez C. Julian B. Belleville P. Popall M. (2005). Applications of hybrid organic-inorganic nanocomposites. J. Mater. Chem. 15, 3559–3592. 10.1039/b509097k Sanfilippo V. Caruso V. C. L. Cucci L. M. Inturri R. Vaccaro S. Satriano C. (2020). Hyaluronan-Metal gold nanoparticle hybrids for targeted tumor cell therapy. Int. J. Mol. Sci. 21 21, 3085. 10.3390/ijms21093085 Sang L. Zhao Y. Burda C. (2014). TiO2 nanoparticles as functional building blocks. Chem. Rev. 114, 9283–9318. 10.1021/cr400629p Saveleva M. S. Eftekhari K. Abalymov A. Douglas T. E. Volodkin D. Parakhonskiy B. V. (2019). Hierarchy of hybrid materials—the place of inorganics-in-organics in it, their composition and applications. Front. Chem. 7, 179. 10.3389/fchem.2019.00179 Selim M. S. Yang H. Wang F. Q. Li X. Huang Y. Fatthallah N. A. (2018). Silicone/Ag@ SiO2 core–shell nanocomposite as a self-cleaning antifouling coating material. RSC Adv. 8, 9910–9921. 10.1039/c8ra00351c Sergeeva A. Sergeev R. Lengert E. Zakharevich A. Parakhonskiy B. Gorin D. (2015). Composite magnetite and protein containing CaCO3 crystals. External manipulation and Vaterite--> calcite recrystallization-mediated release performance. ACS Appl. Mater. interfaces 7, 21315–21325. 10.1021/acsami.5b05848 Sethi R. Lee C. H. (2012). Endothelial progenitor cell capture stent: Safety and effectiveness. J. interventional Cardiol. 25, 493–500. 10.1111/j.1540-8183.2012.00740.x Shahmoradi B. Maleki A. Byrappa K. (2011). Photocatalytic degradation of Amaranth and Brilliant Blue FCF dyes using in situ modified tungsten doped TiO2 hybrid nanoparticles. Catal. Sci. Technol. 1, 1216–1223. 10.1039/c1cy00023c Sharifi M. Attar F. Saboury A. A. Akhtari K. Hooshmand N. Hasan A. (2019). Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and therapy. J. Control. Release Official J. Control. Release Soc. 311-312, 170–189. 10.1016/j.jconrel.2019.08.032 Shavel A. Gaponik N. Eychmüller A. (2004). Efficient UV-blue photoluminescing thiol-stabilized water-soluble alloyed ZnSe (S) nanocrystals. J. Phys. Chem. B 108, 5905–5908. 10.1021/jp037941t Shen N. Yan F. Pang J. Gao Z. Al-Kali A. Haynes C. L. (2018). HDL-AuNPs-BMS nanoparticle conjugates as molecularly targeted therapy for leukemia. ACS Appl. Mater. Interfaces 10, 14454–14462. 10.1021/acsami.8b01696 Shi M. Liu Y. Xu M. Yang H. Wu C. Miyoshi H. (2011). Core/shell Fe3O4 @SiO2 nanoparticles modified with PAH as a vector for EGFP plasmid DNA delivery into HeLa cells. Macromol. Biosci. 11, 1563–1569. 10.1002/mabi.201100150 Shim B. S. Chen W. Doty C. Xu C. Kotov N. A. (2008). Smart electronic yarns and wearable fabrics for human biomonitoring made by carbon nanotube coating with polyelectrolytes. Nano Lett. 8, 4151–4157. 10.1021/nl801495p Sinani V. A. Gheith M. K. Yaroslavov A. A. Rakhnyanskaya A. A. Sun K. Mamedov A. A. (2005). Aqueous dispersions of single-wall and multiwall carbon nanotubes with designed amphiphilic polycations. J. Am. Chem. Soc. 127, 3463–3472. 10.1021/ja045670+ Singh P. Srivastava S. Singh S. K. (2019). Nanosilica: Recent progress in synthesis, functionalization, biocompatibility, and biomedical applications. ACS biomaterials Sci. Eng. 5, 4882–4898. 10.1021/acsbiomaterials.9b00464 Skirtach A. G. Antipov A. A. Shchukin D. G. Sukhorukov G. B. (2004). Remote activation of capsules containing Ag nanoparticles and IR dye by laser light. Langmuir 20, 6988–6992. 10.1021/la048873k Skirtach A. G. Dejugnat C. Braun D. Susha A. S. Rogach A. L. Parak W. J. (2005). The role of metal nanoparticles in remote release of encapsulated materials. Nano Lett. 5, 1371–1377. 10.1021/nl050693n Skirtach A. G. Volodkin D. V. Möhwald H. (2010). Bio-interfaces—interaction of PLL/HA thick films with nanoparticles and microcapsules. ChemPhysChem 11, 822–829. 10.1002/cphc.200900676 Slyusarenko N. Gerasimova M. Plotnikov A. Gaponik N. Slyusareva E. (2019). Photoluminescence properties of self-assembled chitosan-based composites containing semiconductor nanocrystals. Phys. Chem. Chem. Phys. 21, 4831–4838. 10.1039/c8cp07051b Smith B. R. Inglis D. W. Sandnes B. Rabeau J. R. Zvyagin A. V. Gruber D. (2009). Five-nanometer diamond with luminescent nitrogen-vacancy defect centers. small 5, 1649–1653. 10.1002/smll.200801802 Song C. Zhang J. Jiang X. Gan H. Zhu Y. Peng Q. (2021). SPR/SERS dual-mode plasmonic biosensor via catalytic hairpin assembly-induced AuNP network. Biosens. Bioelectron. 190, 113376. 10.1016/j.bios.2021.113376 Song X. J. Gong H. Yin S. N. Cheng L. Wang C. Li Z. W. (2014). Ultra- small iron oxide doped polypyrrole nanoparticles for in vivo multimodal imaging guided photothermal therapy. Adv. Funct. Mater. 24, 1194–1201. 10.1002/adfm.201302463 Stavitskaya A. Rubtsova M. Glotov A. Vinokurov V. Vutolkina A. Fakhrullin R. (2022). Architectural design of core–shell nanotube systems based on aluminosilicate clay. Nanoscale Adv. 4, 2823–2835. 10.1039/d2na00163b Sukhanova A. Bozrova S. Gerasimovich E. Baryshnikova M. Sokolova Z. Samokhvalov P. (2022). Dependence of quantum dot toxicity in vitro on their size, chemical composition, and surface charge. Nanomaterials 12, 2734. 10.3390/nano12162734 Sun A. Huang X. Jiao Y. Wang X. Wen J. (2021a). Construction of biological factor-coated stent and its effect on promoting endothelialization. Mater. Sci. Eng. C 122, 111943. 10.1016/j.msec.2021.111943 Sun B. Chang R. Cao S. Yuan C. Zhao L. Yang H. (2020a). “Acid-activatable transmorphic peptide-based nanomaterials for photodynamic therapy,” Angewandte Chemie Int. Ed. Engl., 59, 20582–20588. 10.1002/anie.202008708 Sun W. Luo L. Feng Y. Qiu Y. Shi C. Meng S. (2020b). Gadolinium–rose bengal coordination polymer nanodots for MR-/Fluorescence-Image-Guided radiation and photodynamic therapy. Adv. Mater. 32, 2000377. 10.1002/adma.202000377 Sun W. S. Yang J. X. Hou M. F. Xie S. W. Xiong L. Q. Li B. (2021b). A nano “immune‐guide” recruiting lymphocytes and modulating the ratio of macrophages from different origins to enhance cancer immunotherapy. Adv. Funct. Mater. 31 31, 2009116. 10.1002/adfm.202009116 Sun W. Zhang X. Jia H.-R. Zhu Y.-X. Guo Y. Gao G. (2019). Water-dispersible candle soot-derived carbon nano-onion clusters for imaging-guided photothermal cancer therapy. Small (Weinheim Der Bergstrasse, Ger. 15, e1804575. 10.1002/smll.201804575 Tambunlertchai S. Srisang S. Nasongkla N. (2017). Erratum to: Development of antimicrobial coating by layer-by-layer dip coating of chlorhexidine-loaded micelles. Medicine 28, 118. 10.1007/s10856-017-5929-0 Tan D. Yuan P. Liu D. Du P. (2016). “Surface modifications of halloysite,” in Nanosized tubular clay minerals (Guangzhou: Halloysite and Imogolite), 167–201. Tan M. Del Rosal B. Zhang Y. Rodríguez E. M. Hu J. Zhou Z. (2018). Rare-earth-doped fluoride nanoparticles with engineered long luminescence lifetime for time-gated in vivo optical imaging in the second biological window. Nanoscale 10, 17771–17780. 10.1039/c8nr02382d Tarakanchikova Y. Muslimov A. Sergeev I. Lepik K. Yolshin N. Goncharenko A. (2020). A highly efficient and safe gene delivery platform based on polyelectrolyte core-shell nanoparticles for hard-to-transfect clinically relevant cell types. J. Mater. Chem. B 8, 9576–9588. 10.1039/d0tb01359e Taubert A. Leroux F. Rabu P. De Zea Bermudez V. (2019). „Advanced hybrid nanomaterials”. Beilstein-Institut). Teepakakorn A. Ogawa M. (2021). Self-healing polymer–clay hybrids by facile complexation of a waterborne polymer with a clay. Mater. Adv. 2, 3770–3776. 10.1039/d1ma00099c Tetsuka H. Ebina T. Nanjo H. Mizukami F. (2007). Highly transparent flexible clay films modified with organic polymer: Structural characterization and intercalation properties. J. Mater. Chem. 17, 3545–3550. 10.1039/b705063a Thaxton C. S. Georganopoulou D. G. Mirkin C. A. (2006). Gold nanoparticle probes for the detection of nucleic acid targets. Clin. Chim. Acta 363, 120–126. 10.1016/j.cccn.2005.05.042 Tomai T. Tang L. Y. Yoko A. Omura Y. Seong G. Adschiri T. (2021). Facile regeneration strategy for facet-controlled nanocatalysts via the dissolution-reprecipitation process promoted by an organic modifier. Chem. Mater. 33, 7780–7784. 10.1021/acs.chemmater.1c02145 Ung T. Liz-Marzán L. M. Mulvaney P. (2001). Optical properties of thin films of Au@ SiO2 particles. J. Phys. Chem. B 105, 3441–3452. 10.1021/jp003500n Uskoković V. Desai T. A. (2014). In vitro analysis of nanoparticulate hydroxyapatite/chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J. Pharm. Sci. 103, 567–579. 10.1002/jps.23824 Venditto V. J. Szoka F. C. Jr (2013). Cancer nanomedicines: So many papers and so few drugs!. Adv. drug Deliv. Rev. 65, 80–88. 10.1016/j.addr.2012.09.038 Vita F. Innocenti C. Secchi A. Albertini F. Grillo V. Fiore A. (2018). Colloidal Au/iron oxide nanocrystal heterostructures: Magnetic, plasmonic and magnetic hyperthermia properties. J. Mater. Chem. C 6, 12329–12340. 10.1039/c8tc01788c Volodkin D. Delcea M. Mohwald H. Skirtach A. (2009). Remote near-IR light activation of a hyaluronic acid/poly (l-lysine) multilayered film and film-entrapped microcapsules. ACS Appl. Mater. interfaces 1, 1705–1710. 10.1021/am900269c Volodkin D. Skirtach A. Möhwald H. (2012). Bioapplications of light-sensitive polymer films and capsules assembled using the layer-by-layer technique. Polym. Int. 61, 673–679. 10.1002/pi.4182 Wan J. Y. Xie J. Kong X. Liu Z. Liu K. Shi F. F. (2019). Ultrathin, flexible, solid polymer composite electrolyte enabled with aligned nanoporous host for lithium batteries. Nat. Nanotechnol. 14, 705–711. 10.1038/s41565-019-0465-3 Wang B. Chen K. Jiang S. Reincke F. Tong W. Wang D. (2006). Chitosan-mediated synthesis of gold nanoparticles on patterned poly (dimethylsiloxane) surfaces. Biomacromolecules 7, 1203–1209. 10.1021/bm060030f Wang C. Ying C. Shang J. Karcher S. E. Mccloy J. Liu J. (2022). A bioinspired coating for stabilizing Li metal batteries. ACS Appl. Mater. Interfaces 14, 43886–43896. 10.1021/acsami.2c10667 Wang D. Wu H. Zhou J. Xu P. Wang C. Shi R. (2018a). In situ one-pot synthesis of MOF–polydopamine hybrid nanogels with enhanced photothermal effect for targeted cancer therapy. Adv. Sci. 5, 1800287. 10.1002/advs.201800287 Wang H. Chen Q. Zhou S. (2018b). Carbon-based hybrid nanogels: A synergistic nanoplatform for combined biosensing, bioimaging, and responsive drug delivery. Chem. Soc. Rev. 47, 4198–4232. 10.1039/c7cs00399d Wang X. Zhang M. Zhang L. Li L. Li S. Wang C. (2017). Designed synthesis of lipid-coated polyacrylic acid/calcium phosphate nanoparticles as dual pH-responsive drug-delivery vehicles for cancer chemotherapy. Chem. (Weinheim Der Bergstrasse, Ger. 23, 6586–6595. 10.1002/chem.201700060 Wang Y. Wei S. (2022). Green fabrication of bioactive silver nanoparticles using Mentha pulegium extract under alkaline: An enhanced anticancer activity. ACS Omega 7, 1494–1504. 10.1021/acsomega.1c06267 Wen C. Broholm M. M. Dong J. Uthuppu B. Jakobsen M. H. Fjordbøge A. S. (2020). Transport of citrate and polymer coated gold nanoparticles (AuNPs) in porous media: Effect of surface property and Darcy velocity. J. Environ. Sci. (China) 92, 235–244. 10.1016/j.jes.2020.02.026 Wubneh A. Tsekoura E. K. Ayranci C. Uludag H. (2018). Current state of fabrication technologies and materials for bone tissue engineering. Acta biomater. 80, 1–30. 10.1016/j.actbio.2018.09.031 Xavier J. R. (2021). Electrochemical and dynamic mechanical studies of newly synthesized polyurethane/SiO2-Al2O3 mixed oxide nanocomposite coated steel immersed in 3.5% NaCl solution. Surfaces Interfaces 22, 100848. 10.1016/j.surfin.2020.100848 Xiao H. Guo Y. Li B. Li X. Wang Y. Han S. (2020). M2-Like tumor-associated macrophage-targeted codelivery of STAT6 inhibitor and IKKβ siRNA induces M2-to-M1 repolarization for cancer immunotherapy with low immune side effects. ACS Central Sci. 6, 1208–1222. 10.1021/acscentsci.9b01235 Xie L. Tong W. Yu D. Xu J. Li J. Gao C. (2012). Bovine serum albumin nanoparticles modified with multilayers and aptamers for pH-responsive and targeted anti-cancer drug delivery. J. Mater. Chem. 22, 6053–6060. 10.1039/c2jm16831f Xie P. G. Ling H. Q. Pang M. He L. Zhuang Z. Y. Zhang G. L. (2022). Umbilical cord mesenchymal stem cells promoting spinal cord injury repair visually monitored by AIE‐tat nanoparticles (adv. Therap. 12/2022). Adv. Ther. 5, 2270028. 10.1002/adtp.202270028 Xiong R. Raemdonck K. Peynshaert K. Lentacker I. De Cock I. Demeester J. (2014). Comparison of gold nanoparticle mediated photoporation: Vapor nanobubbles outperform direct heating for delivering macromolecules in live cells. ACS Nano 8, 6288–6296. 10.1021/nn5017742 Xu B. Li A. Wang R. Zhang J. Ding Y. Pan D. (2021). Elastic janus film for wound dressings: Unidirectional biofluid transport and effectively promoting wound healing. Adv. Funct. Mater. 31, 2105265. 10.1002/adfm.202105265 Xu M. Zhu J. Wang F. Xiong Y. Wu Y. Wang Q. (2016). Improved in vitro and in vivo biocompatibility of graphene oxide through surface modification: Poly(acrylic acid)-functionalization is superior to PEGylation. ACS Nano 10, 3267–3281. 10.1021/acsnano.6b00539 Xu Z. Wang S. Li Y. Wang M. Shi P. Huang X. (2014). Covalent functionalization of graphene oxide with biocompatible poly(ethylene glycol) for delivery of paclitaxel. ACS Appl. Mater. Interfaces 6, 17268–17276. 10.1021/am505308f Yan L. Wang Y. Li J. Kalytchuk S. Susha A. S. Kershaw S. V. (2014). Highly luminescent covalently bonded layered double hydroxide–fluorescent dye nanohybrids. J. Mater. Chem. C 2, 4490–4494. 10.1039/c3tc32483d Yang C. Mi X. Su H. Yang J. Gu Y. Zhang L. (2019). GE11-PDA-Pt@ USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy. Biomaterials Sci. 7, 2076–2090. 10.1039/c8bm01492b Yang R. Zheng Y. Zhang Y. Li G. Xu Y. Zhang Y. (2022). Bipolar metal flexible electrospun fibrous membrane based on metal-organic framework for gradient healing of tendon-to-bone interface regeneration. Adv. Healthc. Mater. 11, 2200072. 10.1002/adhm.202200072 Yang Y. Guo L. Wang Z. Liu P. Liu X. Ding J. (2021a). Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis and Re-polarization. Biomaterials 264, 120390. 10.1016/j.biomaterials.2020.120390 Yang Z. Tu Q. Zhu Y. Luo R. Li X. Xie Y. (2012). Mussel-inspired coating of polydopamine directs endothelial and smooth muscle cell fate for re-endothelialization of vascular devices. Adv. Healthc. Mater. 1, 548–559. 10.1002/adhm.201200073 Yang Z. Xi Y. Bai J. Jiang Z. Wang S. Zhang H. (2021b). Covalent grafting of hyperbranched poly-L-lysine on Ti-based implants achieves dual functions of antibacteria and promoted osteointegration in vivo . Biomaterials 269, 120534. 10.1016/j.biomaterials.2020.120534 Yashchenok A. M. Borisova D. Parakhonskiy B. V. Masic A. Pinchasik B. Möhwald H. (2012). Nanoplasmonic smooth silica versus porous calcium carbonate bead biosensors for detection of biomarkers. Ann. Phys. 524, 723–732. 10.1002/andp.201200158 Yu P. Wang L. Sun F. Xie Y. Liu X. Ma J. (2019). Co Nanoislands rooted on Co–N–C nanosheets as efficient oxygen electrocatalyst for Zn–air batteries. Adv. Mater. 31, 1901666. 10.1002/adma.201901666 Zaheer A. Murshed M. De Grand A. M. Morgan T. G. Karsenty G. Frangioni J. V. (2006). Optical imaging of hydroxyapatite in the calcified vasculature of transgenic animals. Arteriosclerosis, thrombosis, Vasc. Biol. 26, 1132–1136. 10.1161/01.atv.0000210016.89991.2a Zhang D. Peng F. Liu X. (2021a). Protection of magnesium alloys: From physical barrier coating to smart self-healing coating. J. Alloys Compd. 853, 157010. 10.1016/j.jallcom.2020.157010 Zhang G. Yang Z. Lu W. Zhang R. Huang Q. Tian M. (2009). Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. Biomaterials 30, 1928–1936. 10.1016/j.biomaterials.2008.12.038 Zhang L. Bai X. Tian H. Zhong L. Ma C. Zhou Y. (2012a). Synthesis of antibacterial film CTS/PVP/TiO2/Ag for drinking water system. Carbohydr. Polym. 89, 1060–1066. 10.1016/j.carbpol.2012.03.063 Zhang Q. Li N. Goebl J. Lu Z. Yin Y. (2011). A systematic study of the synthesis of silver nanoplates: Is citrate a "magic" reagent? J. Am. Chem. Soc. 133, 18931–18939. 10.1021/ja2080345 Zhang Q. Shen C. Zhao N. Xu F. J. (2017). Redox-responsive and drug-embedded silica nanoparticles with unique self-destruction features for efficient gene/drug codelivery. Adv. Funct. Mater. 27, 1606229. 10.1002/adfm.201606229 Zhang X. Servos M. R. Liu J. (2012b). Ultrahigh nanoparticle stability against salt, pH, and solvent with retained surface accessibility via depletion stabilization. J. Am. Chem. Soc. 134, 9910–9913. 10.1021/ja303787e Zhang Z. Jia J. Lai Y. Ma Y. Weng J. Sun L. (2010). Conjugating folic acid to gold nanoparticles through glutathione for targeting and detecting cancer cells. Bioorg. Med. Chem. 18, 5528–5534. 10.1016/j.bmc.2010.06.045 Zhang Z. Xiao X. Zhou Y. Huang L. Wang Y. Rong Q. (2021b). Bioinspired graphene oxide membranes with pH-responsive nanochannels for high-performance nanofiltration. ACS Nano 15, 13178–13187. 10.1021/acsnano.1c02719 Zhao W. Wei J.-S. Zhang P. Chen J. Kong J.-L. Sun L.-H. (2017). Self-Assembled ZnO nanoparticle capsules for carrying and delivering isotretinoin to cancer cells. ACS Appl. Mater. interfaces 9, 18474–18481. 10.1021/acsami.7b02542 Zheludkevich M. L. Shchukin D. G. Yasakau K. A. Möhwald H. Ferreira M. G. S. (2007). Anticorrosion coatings with self-healing effect based on nanocontainers impregnated with corrosion inhibitor. Chem. Mater. 19, 402–411. 10.1021/cm062066k Zheng T. Perona Martínez F. Storm I. M. Rombouts W. Sprakel J. Schirhagl R. (2017). Recombinant protein polymers for colloidal stabilization and improvement of cellular uptake of diamond nanosensors. Anal. Chem. 89, 12812–12820. 10.1021/acs.analchem.7b03236 Zheng Y. F. Gu X. N. Witte F. (2014). Biodegradable metals. Mater. Sci. Eng. R Rep. 77, 1–34. 10.1016/j.mser.2014.01.001 Zhou C.-H. Shen Z.-F. Liu L.-H. Liu S.-M. (2011). Preparation and functionality of clay-containing films. J. Mater. Chem. 21, 15132–15153. 10.1039/c1jm11479d Zhou Y. Chen Z. Zhao D. Li D. He C. Chen X. (2021). A pH-triggered self-unpacking capsule containing zwitterionic hydrogel-coated MOF nanoparticles for efficient oral exendin-4 delivery. Adv. Mater. Deerf. Beach, Fla.) 33, e2102044. 10.1002/adma.202102044 Zhu A. Ali S. Xu Y. Ouyang Q. Chen Q. (2021). A SERS aptasensor based on AuNPs functionalized PDMS film for selective and sensitive detection of Staphylococcus aureus . Biosens. Bioelectron. 172, 112806. 10.1016/j.bios.2020.112806 Zuaznabar-Gardona J. C. Fragoso A. (2018). A wide-range solid state potentiometric pH sensor based on poly-dopamine coated carbon nano-onion electrodes. Sensors and actuators B:. Chemical 273, 664–671. Glossary α-CHC

α-cyano-4-hydroxycinnamic acid

 AHAPS

N-(6-aminohexyl)-3-aminopropyltrimethoxy silane

 ALP

alkaline phosphatase

 APTES

3-aminopropyltriethoxysilane

 BPEI

branched polyethylene-imine

 CDxs

Cyclodextrins

 CHA

catalytic hairpin assembly

 CNO

carbon nano-onion

 CQDs

carbon quantum dots

 CTAB

cetyltrimethylammonium bromide

 CTS

Chitosan

 DDA

dodecyl amine

 DMAP

4-(dimethylamino)pyridine

 GO

graphene oxide

 GLU

glutaraldehyde

 Ha

hyaluronic acid

 HA

hydroxyapatite

 HAD

hexadecyl amine

 HDL

high-density lipoprotein

 HDTMA

Hexadecyl trimethy-lammonium bromide

 MCT-β-CD

Monochlorotriazinyl-β-cyclodextrin

 MOF

Organic Framework

 MWCNTs

multi-walled carbon nanotubes

 PAA

polyacrylic acid

 PAH

poly(allylamine hydrochloride)

 PC

Phosphorylcholine

 PCL

poly(caprolactone)

 PDA

polydopamine

 PDDA

poly (diallyl dimethyl ammonium chloride)

 PDMS

polydimethylsiloxane

 PE

polyethene

 PEA

poly(ester-amide)

 PDMS

polydimethylsiloxane

 PEEK

polyetheretherketone

 PEG

poly(ethylene glycol)

 PEI

polyethyleneimine

 PEO

poly ethylene oxide

 PEVA

Polyethylene-co-vinyl acetate

 PLA

Polylactic acid

 PLL

poly(L-lysine)

 PMDA

Pyromellitic dianhydride

 PMMA

poly(methyl methacrylate)

 PMPC

polymethacryloyloxyethyl phosphorylcholine

 POM

Polyoxymethylene

 PSS

poly(sodium styrenesulfonate)

 PU

Polyurethane

 PUR

Polyurethane

 PVP

polyvinyl pyrrolidone

 PVDF

poly (vinylidene fluoride)

 SPA

polyacrylate

 SS

stainless steels

 TOPO

trioctylphosphine oxide