Superparamagnetic iron oxide nanoparticles (SPIONs) are nanoscale particles composed of iron and oxygen, exhibiting magnetic properties that can be controlled and used for various applications such as biomedical imaging (Kandasamy and Maity, 2015). SPIONs are recognized for their T2 contrast attributes, rendering them appropriate for augmenting tissue contrast in MRI (Caspani et al., 2020). Their biocompatibility, stability, and superparamagnetism under magnetic fields have been exhaustively examined, increasing their attractiveness for biomedical implementations (Wei et al., 2021). Moreover, SPIONs have been explored for a range of applications, including targeted drug delivery, cellular engineering, and cell tracking (Singh et al., 2010; Deng et al., 2022). As well, SPIONs have found use as contrast agents in MRI, where their superparamagnetism creates an uneven local magnetic field that leads to shortened T2 values on MRI (Hua et al., 2015). The possible toxicity of SPIONs has also been researched, stressing the need to comprehend their biological impacts (Veiseh et al., 2013).

In the context of MRI, SPIONs have demonstrated efficacy as contrast agents, notably when engulfed by macrophages in target tissues. They impact the relaxation rate of water, thereby enhancing MRI contrast (LaConte et al., 2007; Daldrup-Link et al., 2011). Additionally, the creation of SPIO-based nanovectors for in vivo MRI holds particular interest due to their safe toxicity profile and magnetic characteristics (Veiseh et al., 2013). Furthermore, the employment of SPIONs for targeted diagnosis and therapy in cancers, such as pancreatic cancer, has been explored, emphasizing their potential in medical applications (Figure 3) (Mahmoudi et al., 2011; Demortiere et al., 2011; Serkova, 2017). Various studies have reported the design of SPIO-loaded phospholipid micelles, showcasing the versatility of SPIONs across different delivery systems (Fathy et al., 2019; Cai et al., 2020). Specific findings indicate that PEGylated SPIO nanoparticles exhibit excellent relaxivity and stability, with distinct imaging characteristics depending on the magnetic field strength. For example, 8-nanometer SPIO@PEG5k functions effectively as a T2 contrast agent at 3.0 T and as a dual-mode agent at lower strengths, while 4-nanometer variants are suitable for similar roles at various field strengths (Deng et al., 2021). Additionally, SPIOs with a 14-nanometer core and PEG1000 coating demonstrate a remarkable T2 relaxivity of 385 s^-1 mM^-1, indicating high efficiency per iron atom and significant potential for in vivo tumor imaging (Tong et al., 2010). Furthermore, a novel non-gadolinium-based nanoscale contrast agent, SPIO@[Mn (Dopa-EDTA)]2−, has shown promising MRI performance across different magnetic fields, particularly as a dual-modality agent for imaging human organs and blood vessels (Wu et al., 2020).

SPIONs have been extensively researched for their role as contrast agents in MRI (Li et al., 2017). Reports indicate successful incorporation of Doxorubicin along with clusters of SPIONs within micelle cores (Nasongkla et al., 2006). SPIONs are commercially available and have FDA-approval for use in humans (Mailänder et al., 2008). Due to their good biocompatibility and excellent MRI properties, SPIONs are widely utilized in theranostic applications (Yuan et al., 2018). Development efforts have focused on multifunctional, water-soluble SPIONs designed for targeted drug delivery and dual-modality imaging of tumors expressing integrin αvβ3, using PET/MRI techniques (Yang et al., 2011). SPIONs are unique medical nanomaterials with super-magnetic, surface modification, and targeting capabilities. For cell labeling, SPIONs with sizes ranging from 80 to 180 nm are frequently used as T2 and T2*-shortening MRI contrast agents (Skachkov et al., 2018). These multifunctional nanoparticles, referred to as SPIONs-Au, exhibit superparamagnetic properties and have substantial absorbance in the Near-Infrared range of the electromagnetic spectrum (Ji et al., 2007). SPIONs have been widely applied in MRI for imaging blood vessels and tumors, surpassing Gd-based agents (Lu et al., 2014). SPIONs are becoming viable options for nanomedicine focused on tumor imaging and targeted drug delivery for cancer treatment (Zou et al., 2010). With their unique paramagnetic characteristics, they can function as contrast agents across various parametric MRI techniques, including T2 and susceptibility-weighted imaging (Lee et al., 2021). Additionally, SPIO holds great potential for developing smart MRI probes aimed at cell dynamics tracking (Toyota et al., 2012). SPIONs can effectively label neural precursor cells and hematopoietic stem cells (Hu et al., 2009).

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) have core diameters of less than 5.0 nm and are anticipated to represent a new class of contrast agents. Their promising application stems from their enhanced MRI performance, prolonged circulation time in the bloodstream after suitable surface modifications, ability for renal clearance, and outstanding biosafety profile (Wang et al., 2017; Si et al., 2022). This makes them particularly promising for usage in MRI, a technique known for providing detailed morphological and functional information about atheromatous plaques (Sadat et al., 2017).

These iron oxide agents exhibit signal loss that depends on their concentration in T2-and T2*-weighted MRI sequences, positioning them as potential future contrast agents for patients susceptible to nephrogenic systemic fibrosis (Neuwelt et al., 2009). Macrophages, the predominant inflammatory cells found in stroke lesions, can be effectively detected using USPIONs as a cell-selective MRI agent (Saleh et al., 2004). In research focused on inflammatory responses following ischemic strokes, USPIONs were administered after MRI scans conducted on day 6 (DeLong et al., 2022).

Furthermore, USPIO nanoparticles have sparked interest as potential MRI contrast agents in tumor diagnosis (Wang et al., 2023). Monodisperse USPIONs cores, produced via the thermal decomposition of iron (III)-oleate precursor, have been designed as gadolinium-free T1 contrast agents for vascular imaging (Khandhar et al., 2018). A study examined the effectiveness of R2* and quantitative susceptibility mapping in quantitatively evaluating the accumulation of USPIONs particles in the arcAβ mouse model of cerebral amyloidosis (Klohs et al., 2016). Optimized USPIO contrast agents, designed for uptake by the mononuclear phagocytic system, are gaining increasing attention within translational cardiovascular research (Morris et al., 2008).

Iron oxide nanoparticles (Fe₃O₄ NPs) are utilized in MRI as contrast agents, leveraging their magnetic characteristics to enhance imaging quality and enable the visualization of specific tissues or organs with increased sensitivity and specificity. Iron oxide nanoparticles, specifically Fe₃O₄, have sparked significant interest due to their potential utility as MRI contrast agents. Study has demonstrated that Fe₃O₄ NPs effectively enhance contrast in T2-weighted MRI images (Shou et al., 2020). Moreover, due to their magnetic characteristics and biological compatibility, Fe₃O₄ NPs have found extensive use in drug delivery and MRI (Zhang X. et al., 2016).

Explorations into biofunctionalization of Fe₃O₄ NPs have opened new avenues for applications in magnetic hyperthermia and MRI (Hayashi et al., 2010). Furthermore, highly-magnetic iron carbide nanoparticles have shown promise as potent T2 contrast agents, suggesting the possibilities for Fe₃O₄-based contrast agents in MRI (Huang et al., 2014a). Fe₃O₄ mesoporous carbon nanoparticles have been engineered as efficient tumor-targeting nanocarriers for enhancing chemotherapy and photothermal therapy, underscoring their potential in cancer treatment and imaging (Qian et al., 2021). In this context, recent research investigates a novel approach to conjugate modified gefitinib, a primary medication for non-small cell lung cancer, with Fe₃O₄ NPs to improve the delivery efficiency of chemotherapy drugs. The study aims to examine how the drug is absorbed in the inner and outer regions of tumors using MRI guidance, with the goal of achieving more effective cancer treatments. This dual application of Fe₃O₄ NPs highlights their versatility in both enhancing imaging techniques and facilitating targeted drug delivery, ultimately contributing to improved outcomes in cancer therapy (Thangudu et al., 2023).

Moreover, research has delved into the role of Fe₃O₄ mesoporous carbon nanoparticles in MRI enhancement and hyperthermia for cancer treatment (Lu et al., 2021). Investigations have also centered on the optical and magnetic characteristics of superparamagnetic Fe₃O₄ mesoporous carbon nanoparticles, illustrating their potential across various applications, including MRI (Xie et al., 2024). Molecular dynamics simulation studies have furnished insights into the adsorption of diverse biopolymers on Fe₃O₄ mesoporous carbon nanoparticles, further enriching our understanding of their potential as MRI contrast agents (Zheng et al., 2021). Additionally, magnetic particle imaging has been studied for cell tracking, with superparamagnetic iron oxide nanoparticles, including Fe₃O₄ mesoporous carbon nanoparticles, being prevalently used for this purpose (Sehl et al., 2020).

Manganese oxide nanoparticles (MnO NPs) have garnered significant interest as potential contrast agents for MRI, due to their unique characteristics that position them as apt candidates for enhancing imaging capabilities. Nano-encapsulated manganese oxide (NEMO) particles exhibit properties like pH-switchable signals, high metal loading capacity, and targeting capabilities that render them ideal for specific imaging applications (Martinez de la Torre et al., 2023). Inorganic manganese oxide particles and manganese carbonate have demonstrated versatility in molecular and cellular MRI as convertible contrast agents. Their effectiveness as T1 MRI contrast agents for preclinical research further underscores their potential in diagnostic imaging (Poon et al., 2021).

Manganese-based nanostructures’ responsiveness as MRI contrast agents allows tunable performance for enhanced imaging capabilities in medical diagnostics (García-Hevia et al., 2019). The creation of theranostic liposomes modified with the AS1411 aptamer, which co-encapsulate manganese oxide nano-contrast agents and paclitaxel, presents an innovative approach for cancer imaging and treatment (Li et al., 2019). Studies have demonstrated that folic acid-modified Mn₃O₄@SiO₂ nanoparticles exhibit high colloidal stability and effective targeting of HeLa cells, leading to significant tumor accumulation and enhanced MRI signals (Yang et al., 2014). Similarly, H-MnO₂-PEG/C&D nanoparticles decompose in acidic environments to release drugs while significantly improving T1 contrast in MRI, showcasing their potential for passive tumor targeting and synergistic therapeutic effects through combined chemotherapy and photodynamic therapy (Yang et al., 2017). Furthermore, FA-Mn₃O₄@PDA@PEG nanoparticles exhibit an ultrahigh longitudinal relaxivity of 14.47 mM ^-1s^-1—nearly three times that of commercial agents—demonstrating their efficacy as both MRI contrast agents and therapeutic platforms under near-infrared laser irradiation (Ding et al., 2016). Manganese oxide nanostructures have shown high signal enhancements and responsiveness as MRI contrast media, demonstrating their prospective in vitro imaging techniques (Bañobre-López et al., 2018).

Manganese-engineered iron oxide nanoparticles' paramagnetic properties have facilitated the tunability of T1 and T2 contrast abilities, leading to the development of versatile MRI contrast agents with superior imaging capabilities (Huang et al., 2014b). Lipid-micelle-based theranostics loaded with manganese have been studied for their ability to deliver drugs and genes to the lungs simultaneously, highlighting the potential of manganese compounds as multifunctional agents for both imaging and therapeutic uses (Howell et al., 2013). Additionally, research into fruit juices high in manganese ions as oral contrast media for MRI imaging of the gastrointestinal tract illustrates the various sources of manganese-based contrast media (Rizzo et al., 2021).

Carbon nanotubes (CNTs), composed solely of carbon atoms and structured into cylindrical shapes, are renowned for their extraordinary robustness, elevated electrical conductivity, as well as distinct mechanical and thermal attributes (Zhang et al., 2021). In the realm of MRI, CNTs have risen to prominence given their potential to enhance contrast agents, thus improving image precision and allowing superior tissue and organ visualization. These nanotubes encompass single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), both attracting significant research attention (Deshmukh et al., 2020; Tomczyk et al., 2020). To further augment their magnetic properties and suitability for MRI contrast enhancement, strategies such as integrating materials like gadolinium nanoparticles into carbon nanotubes have been undertaken (Gizzatov et al., 2015). MWCNTs, with their distinguished magnetic and electronic traits, morphology, and capability to breach cell membranes, stand out as attractive candidates for MRI contrast agents (Maciejewska et al., 2015).

Research indicates that the encapsulation of gadolinium ions within carbon nanotubes can amplify MRI contrast for cellular imaging. This highlights the potential role of these nanotubes in propelling further advancements in imaging technologies (Marangon et al., 2014). Additionally, modifying carbon nanotubes with specific ligands, such as hyaluronic acid, could facilitate targeted delivery of contrast agents to tumorous cells, thereby enhancing MRI’s diagnostic abilities (Hou et al., 2015). The synthesis of carbon nanotubes with other materials like iron oxide nanoparticles brought about the creation of dual-functional contrast media suitable for MRI and alternate imaging modalities, thus accentuating the adaptability of carbon nanotubes in a range of multimodal imaging applications (Wang et al., 2014).

Fullerenes are carbon-based molecules with a cage-like structure, typically formed in spherical or tubular shapes. They exhibit distinct characteristics, including remarkable stability and strong antioxidant properties (Minami et al., 2021). For instance, one study highlights the use of water-soluble endohedral fullerenes as MRI contrast media, showcasing intriguing aspects of this research (Dunsch and Yang, 2007). In addition, work by Ghiassi et al. discusses the use of gadolinium-loaded endohedral fullerenes as effective relaxation agents for MRI, further emphasizing their potential for biomedical imaging applications (Ghiassi et al., 2014). Moreover, research by Shu et al. presents a straightforward preparation of a novel gadofullerene-based MRI contrast media with high relaxivity, spotlighting the potential of fullerenes for enhancing MRI contrast (Shu et al., 2009). The studies also offer insights into the preparation, functional modifications, and life science applications of fullerenes, particularly in context of MRI contrast enhancement. The potential of fullerenes for tumor imaging, drug delivery, and antioxidant capability has also been discussed, further accentuating their multifunctional capabilities and potential for biomedical applications (Gaur et al., 2021; Alosaimi et al., 2023). Furthermore, these studies address the challenges and opportunities related to using fullerenes as MRI contrast media, emphasizing their unique physical characteristics and potential technological uses in medical imaging (Bolskar et al., 2003).

Graphene consists of a single layer of carbon atoms organized in a two-dimensional honeycomb lattice, recognized for its remarkable strength, electrical conductivity, and transparency. Hybrid nanomaterials based on graphene have been utilized in various diagnostic imaging techniques, including fluorescent imaging, MRI, CT scans, and radionuclide imaging (Akinwande et al., 2017). Hybrid nanoparticles of Mn₃O₄–PDA–graphene quantum dot have demonstrated potential for T1-weighted MRI and optical imaging-assisted photodynamic therapy (Cheng et al., 2019). Earlier research has suggested that Mn²⁺ carbon nanostructure complexes made from graphene oxide nanoplatelets can function effectively as MRI contrast media (Xiao et al., 2016). The superior transmittance and photoluminescence behaviors make graphene a highly appealing nanomaterial for applications in MRI and biomedical imaging (Cheng et al., 2019). Graphene’s potential for diverse, electromagnetic-transparent electronics in medical imaging and diagnostics goes beyond that of conventional metal electrodes (Tweedie et al., 2020). Moreover, by incorporating specific polar C─F bonds into the small-sized graphene oxide framework, a highly water-soluble nanoprobe with exceptional MRI capabilities has been created, providing high-resolution anatomical information in MRI (Xu et al., 2024). Coating copper microelectrodes with graphene has been shown to reduce toxicity, allowing for the development of MRI-compatible neuroelectrodes (Fairfield, 2018).

Silicon nanoparticles are tiny particles made of silicon, recognized for their distinct optical and electronic characteristics, which render them ideal for various applications, including use as contrast agents and in biomedicine. Studies have indicated their effectiveness in enhancing near-infrared (NIR) imaging in ophthalmology (Ki et al., 2024). The development of hyperpolarized silicon nanoparticles has been recognized as a significant advancement for MRI-based biomedical imaging (Hu et al., 2018). Moreover, the utilization of fluorinated silicon nanoparticles has exhibited promise in cancer detection through 19F MRI and fluorescence imaging (Li et al., 2018). The distinctive characteristics of silicon nanoparticles, such as long T1 relaxation times, have facilitated in vivo hyperpolarized silicon MRI with extended imaging durations (Zhang Y. et al., 2016). Additionally, the hyperpolarization of silicon particles using dynamic nuclear polarization (DNP) has notably increased their MRI signals, rendering them effective contrast agents for in vivo MRI (Lin et al., 2021). Silicon nanoparticles have been investigated for their promise as background-free MRI contrast agents, owing to their biological compatibility and adaptable surface chemistry (Seo et al., 2018). Despite the progress made, challenges persist in the development of silicon nanoparticles for MRI applications, including issues related to morphology, size regulation, dispersal, and surface alterations (Luu et al., 2022). Nevertheless, the extended spin-lattice relaxation times displayed by hyperpolarized silicon particles make them intriguing candidates for innovative MRI probes (Kwiatkowski et al., 2017).

Carbon quantum dots (CQDs) are nanoscale carbon particles known for their unique optical properties, which make them applicable in numerous fields, including biology, medicine, and electronics. CQDs have attracted significant attention as potential MRI contrast media due to their distinctive characteristics. The role of Gd-doped CQDs as positive MRI contrast media has been underscored, revealing their potential in enhancing imaging sites (Atabaev, 2018). Furthermore, there’s an inference that CQDs are less prone to stimulate bacterial resistance than antibiotics, positing them as appealing options for extensive clinical application (Wu et al., 2021).

Expanding beyond imaging, the potential of CQDs in visible-light-activated bactericidal functions has been examined, signifying their broad-ranging applications (Meziani et al., 2016). Moreover, owing to their excellent conductivity, small size, and ability to accommodate various functional groups, CQDs have emerged as viable electroactive nanomaterials, positioning them as promising candidates for supercapacitor applications (Prasath et al., 2018). However, careful scrutiny is required towards the cytotoxicity of CQDs and their implications for cell imaging if they are to be utilized as cell imaging agents (Wang et al., 2011).

CQDs, particularly those smaller than 10 nm, are considered promising for microbial imaging, detection, and inactivation due to their outstanding optical properties, customizable surfaces, and good biocompatibility (Lin et al., 2019). Additionally, the synthesis of Gd-doped CQDs presents potential as multi-purpose imaging probes and MRI contrast media for clinical assessment and neuroimaging (Molaei, 2022). Additionally, the production of CQDs via hydrothermal treatment is proposed as a novel strategy to boost diaCEST contrast efficiency, thereby broadening the scope of CQDs in MRI (Pandey et al., 2022). The hydrophilicity of C-dots and the abundance of exchangeable protons on their surface have been noted to transform them into effective diaCEST MRI contrast agents, underlining their adaptability in multimodal imaging (Zhang et al., 2019).

Gadolinium-doped quantum dots (Gd-QDs) are nanoscale semiconductor particles doped with gadolinium, which exhibit enhanced magnetic properties and can be used for imaging and diagnostic applications. Research on gadolinium-based nanoparticles, such as Gd₂O₃, GdF₃, and GdPO₄, has demonstrated their potential effectiveness as contrast agents for MRI (Na et al., 2009). Furthermore, the development of gadolinium-based contrast agents linked to specific ligands, such as aptamers and peptides, provides promising opportunities for improved detection of biomarkers like amyloid-β oligomers, which are important in Alzheimer’s disease (Kim et al., 2023; Yu et al., 2021). Additionally, the synthesis of water-dispersible Gd₂O₃/graphene oxide nanocomposites has indicated an increase in MRI T1 relaxivity, spotlighting the potential for innovative contrast agent designs (Wang et al., 2015). The search for better MRI contrast media has prompted studies on macromolecular ligands, which show significantly higher relaxivity than standard commercial Gd³⁺ MRI agents (Li et al., 2012). Moreover, research is focused on creating biodegradable macromolecular MRI contrast media to facilitate the excretion of Gd(III) chelates after MRI scans, addressing worries about gadolinium retention in the body (Wu et al., 2009). Investigations into polymer micelles embellished with gadolinium complexes aim to enhance MRI sensitivity for advanced imaging applications (Grogna et al., 2010). Despite the common use of Gd-based contrast media for their T1 enhancement properties, significant concerns regarding potential toxicity and gadolinium retention in the body persist. Studies have detected gadolinium accumulation in the brains and kidneys of individuals who have received these MRI contrast media, highlighting the need for safer and more biocompatible alternatives (DeAguero et al., 2023).

Manganese-doped quantum dots (Mn-QDs) are nanoscale semiconductor particles doped with manganese ions, which impart unique optical and magnetic properties for applications such as imaging and sensing. The distinctive properties of these Mn-QDs, including their fluorescent and magnetic traits, render them appealing for dual-mode imaging applications (Zhou et al., 2018). Particularly, Mn-doped ZnSe QDs have been investigated for their potential in fluorescence/MRI dual-mode imaging, underscoring their suitability for bio-imaging applications (Zhou et al., 2018). Moreover, the ability of Mn-QDs to provide contrast enhancement for both T1-and T2-weighted MRI positions them as versatile candidates for multimodal imaging (Kunuku et al., 2023). Studies on the synthesis of highly luminescent surface Mn²⁺-doped CdTe QDs indicate their potential as multimodal contrast agents that can be used for both fluorescence imaging and MRI (Zhang et al., 2014). Further bolstering the potential of Mn-doped QDs as contrast agents is their magnetic behavior, which makes them apt for light-handled spin-based operations (Echeverría-Arrondo et al., 2009). Additionally, the sensitized chemiluminescence reaction between hydrogen peroxide and periodate of various types of Mn-doped ZnS QDs underscores their potential for diverse bioimaging applications. The multifunctionality of Mn-QDs, offering both fluorescence and magnetic resonance properties, heralds them as promising candidates for advanced imaging modalities (Gharghani et al., 2021).