Engineered nanomaterials (NMs) have gained the utmost importance in daily life and have been used in cosmetics, food packaging materials, biosensors, drug delivery systems, and therapies. Subsequently, their size is similar to that of biological macromolecules with antibacterial and anti-odor properties, which can be widely used in wound dressing, antimicrobial coatings, and detergents. However, despite innumerable applications, the biodegradation of NPs and the effect of their accumulation in the environment remain questionable. The accumulation of bio-degraded NPs within cells leads to intracellular changes, causing alterations in organelle integrity or gene alterations. Although NMs continue to be used extensively, it is important to address their toxicity, environmental impact, and possible undesirable side effects ( Figure 1 ). In cancer nanotechnology, monoclonal antibodies, peptides, or small molecules targeting tumor ligands can be induced using NPs to target tumor antigens and tumor vasculature with high specificity and affinity. Recent developments have used bioaffinity NP probes for cellular and molecular imaging to target NP drugs for the treatment of cancers and integrated nanodevices for the early detection of cancers (Gao et al., 2004). Currently, green synthesis of nanoparticles is a novel alternative method. In addition, nanoparticles conjugated with natural biomolecules, which are easily taken up by human cells, have been reported to be more efficacious. In parallel, they act as reducers and stabilizers with smaller sizes and higher penetrating capacities proving themselves to have excellent therapeutic activity.

Green synthesis of metallic NPs from various plant parts, such as leaves, stems, roots, and seeds, is the simple, inexpensive, and reproducible. However, plants as natural sources will certainly produce the added advantage of stable metal NPs. Hence, green-synthesized NPs have proven to be the best candidates for fast and large-scale production in comparison to microbes that require specific environmental conditions (Kalaiarasi et al., 2010). Extracts from the seeds, fruits, leaves, stems of different herbs and higher plants are rich in antioxidants that help boost the capacity of NPs. Therefore, the use of plant-based phytochemicals for the synthesis of NPs unites natural/plant sciences and nanotechnology, and enables safe, environmentally friendly, justifiable, and economically feasible green technologies (Mayegowda et al., 2022a; Mayegowda et al., 2023).

NPs also exhibit antibacterial properties. Silver (Ag) NPs continuously release Ag ions that adhere to the bacterial cell wall and cell membrane, leading to disruption of the bacterial envelope (Khorrami et al., 2018). Once inside the cell, Ag deactivates respiratory enzymes by producing reactive oxygen species (ROS) (Ramkumar et al., 2017). The accumulation of ROS causes damage to DNA, RNA, and proteins, resulting in cell death. The Ag released from NPs binds the sulfur and phosphorus of DNA and blocks replication and cell division, eventually leading to cell death. Ag ions also cause denaturation of ribosomes in the cytoplasm, leading to inhibition of protein synthesis (Durán et al., 2016; Jadimurthy et al., 2022) ( Figure 3 ).

The accumulation of AgNPs alters the structure of the cell membrane and promotes cell lysis (Liao et al., 2019). The surface charge of the NP plays a significant role in determining its interaction with the cell membrane. Cationic NPs infiltrate cells and cause extensive damage. Although anionic NPs do not penetrate the plasma membrane, they destabilize at specific concentrations. While this property of charged NPs suggests potential damage to human cells, it offers opportunities for use as a vehicle for drug delivery to cancerous cells. Denaturation of the cytoplasmic membrane often leads to the rupture of organelles, which ultimately results in cell lysis. Bacterial signal transduction involves phosphorylation events that enable bacteria to sense, adapt, and respond to environmental changes. NPs cause dephosphorylation and disruption of signal transduction, leading to apoptosis (Li et al., 2019). Ag NPs are spherical or quasi spherical and can easily release Ag ions owing to their large surface (Shanmuganathan et al., 2018). To avoid agglomeration, capping agents are used to coat the NPs, which modifies their surfaces and affects their dissolution. The presence of organic or inorganic in the medium can also be responsible for the dissolution of NPs by aggregation.

It has been demonstrated that Ag NPs release Ag ions in the aqueous solution and this is quite faster when the pH is acidic (below 5) than in neutral solution (Jacob et al., 2019). Differential mode of action for NPs has been reported for Gram-positive and Gram-negative bacteria and has been attributed to the presence of peptidoglycan in Gram-positive bacteria which hinders efficient penetration (Meikle et al., 2020). NPs with a size less than 10 nm can directly penetrate the cell and alter cell permeability, enter bacteria, and cause cellular destruction, suggesting a direct correlation between NP uptake and antibacterial properties (Noronha et al., 2017). Hence, Ag NPs have a great potential as antibacterial agents. However, the application of Ag NPs as biofilm inhibitors warrants further investigation (Pugazhendhi et al., 2018). Magnesium oxide NPs have been reported to possess anti-biofilm and anti-adhesion potential, which are efficient against drug-resistant bacteria (Hayat et al., 2018).

Repetitive damage to the environment due to hazardous chemicals, such as excessive use of pesticides, poses a great threat to agriculture worldwide. The use of NPs to target plant pathogens appears to be a safe alternative to chemically synthesized pesticides (Kim et al., 2012). Ag NPs, with varied modes of action, are suggested to be safe agents against plant pathogens, particularly commercially relevant fungal pathogens, as compared to artificial antifungal agent (Manjula et al., 2023). Metal NPs are non-toxic, eco-friendly, and widely used as disinfectants and investigational antifungal mediators (Borehalli Mayegowda et al., 2022). Zinc NPs have potential applications in the pharmaceutical sector, as potent antimicrobial agents and in water disinfection. Studies demonstrating the antifungal activity of Ag NPs are limited. Kim and colleagues have however, suggested a concentration dependent inhibitory activity, probably due to saturation of fungal hyphae with higher density NPs leading to deactivation of the disease-causing fungi (Kim et al., 2012).

While the effect of Ag ions on fungi is limited, reports suggest their inhibitory effect on DNA replication (Feng et al., 2000) and impairment of ribosomal attachment, blocking protein synthesis, enzymes, and additional proteins involved in the production of ATP (Yamanaka et al., 2005). Ag NPs synthesized using ribose sugar and sodium dodecyl sulfate acting like reducing agent and capping agent, respectively demonstrating antifungal activity against highly resistant human pathogenic fungi such as Candida albicans and Candida tropicalis (Mallmann et al., 2015). Similar results have been reported by other researchers (Kim et al., 2009). Fungal cells maintain an ion gradient, trehalose and glucose protects the biological viability of cells from protein denaturation caused by environmental stress such as heat, cold, high pH, dehydration, oxidative stress, and lethal agents (Alvarez-Peral et al., 2002). NPs disrupt the membrane structure and permeability, leading to leakage of intracellular contents and loss of membrane potential. TEM observations revealed the formation of pits in the fungal membrane when treated with Ag ions, leading to cell cycle arrest and cell death in C. albicans. Additionally, destruction of the membrane and inhibition of budding have been noted (Endo et al., 1997). Palladium NPs demonstrated effective antifungal activity against Colletotrichum gloeosporioides and F. oxysporum although in a size-dependent manner (Osonga et al., 2020). Therefore, NPs may induce antifungal activity by disrupting cellular integrity, generating reactive species, and creating osmotic imbalances in pathogens.

While several viral diseases have been eradicated, emerging threats from novel viruses cannot be ignored because of their adaptability and mutagenic ability (Esteban, 2010). Hence, these viruses pose a continuous challenge to the scientific community. Enfuvirtide is a synthetic peptide drug, approved by the US Food and Drug Administration that targets a specific HIV protein named the gp41 coding envelope protein and prevents its fusion (Galdiero et al., 2011).

Under such challenging circumstances, NPs have been developed as promising antiviral agents owing to their increased surface area and unique chemical and physical properties (Elechiguerra et al., 2005). NPs block viral infections by having their mode of action at the time of attachment as well as entry by obstructing polyvalent interactions across viral surface components in interaction with host cell membrane receptors ( Figure 4 ) (Helenius, 2007). Previous studies have demonstrated the efficacy of NPs against HIV-1 (Lara et al., 2010a; Lara et al., 2010b), hepatitis B virus (Lu et al., 2008), herpes simplex virus type 1 (Baram-Pinto et al., 2009), monkey pox virus (Rogers et al., 2008), and influenza virus (Papp et al., 2010). While the interaction and efficacy of NPs against viruses were largely dependent on NP size, they also interacted at specific sites. NPs also bind strongly to the sulfur-containing residues of GP120 (Lara et al., 2010a). Both Ag and Au NPs have promising antiviral properties, particularly against enveloped DNA/RNA viruses. A recent study on COVID-19 viral disease explains about the neurotropism property demonstrating the application of NPs by inhibiting replication by cellular transcytosis blockade when given in the form of encapuslted particles (Ren et al., 2021).

In agriculture, nanotechnology is primarily used for the synthesis of pesticides and fertilizers. NPs can be used as fertilizers to facilitate crop improvement, seed germination, and root growth, while also reducing eco-toxicity. Ag NPs were shown to improve wheat growth and yield. One of the essential micronutrients for plant metabolic processes is zinc, which is involved in the synthesis of auxins such as indole acetic acid and carbohydrates, and in the formation of chlorophyll. Many NPs have been used in the form of pesticides, such as green peach aphids (Ghidan et al., 2018; Mayegowda et al., 2022b). Decreased plant mortality for granulomatosis with polyangiitis (GPA), a condition in which the blood vessels become swollen, was achieved by the synthesis of NPs using aqueous peel extracts of Punica granatum, leaf extracts of Olea europaea, and flower extract of Chamaemelum nobile. GPA infection and the absence of metal accumulation suggest the advantages of bio-NPs (Ghidan et al., 2017). Ag NPs also function as fungicides and have been effective against C. gloeosporioides which causes bitter rot in various crops (Aguilar-Méndez et al., 2010).

Nanotechnology in the food industry can escalate their shelf life of various foods and reduce their depletion due to contagious infestation (Pradhan et al., 2015). Encapsulation of biomolecules, such as lipids proteins, carbohydrates, and vitamins, using NPs can protect them from the acidic environment of the stomach and intestine and can improve their assimilation (Singh et al., 2017). However, the use of NPs in food packaging materials aids in the preservation and protection from several of these issues.

Essential oils obtained from organic compounds, organic acids, and bacteriocins have been extensively studied for use in polymeric matrices as antimicrobial packaging material (Gálvez et al., 2007). Many NPs, such as Ag, copper, biopolymer chitosan, and metal-oxide derived NPs, such as titanium oxide (TiO₂) and zinc oxide (ZnO), have been shown to have antibacterial activity (Manjula et al., 2022). Nanobiosensors are used in the food industry for pathogen detection during processing (Mayegowda et al., 2022). Nano-biosensor can detect changes in the environment, such as moisture content or temperature fluctuations in storage rooms, microbial contamination, or product deprivation. NPs play a vital a role in the food industry, and their green synthesis offers additional advantages.

The use of NPs is most popular in the cosmetic industry. Leading brands such as L’Oreal, Avon, and Johnson and Johnson have patents on nanoparticles. NPs are employed in sunscreens, skin creams, skin lotions, and dye-based products such as fabric colors, skin tanning, and whitening lotions. Sunscreens are used as UV filters and provide broad UV protection with minimal or no adverse effects. NMs labeled in cosmetics can be similar to vesicles in cells, such as liposomes, nano-emulsions, and nano-capsules. Other solid lipid NP conjugates, include nanocrystals and NP with metal-like nanosilver and nanogold, dendrimers, cubosomes, liquid-based hydrogels, and buckyballs (Raj et al., 2012; Ananda et al., 2022). NPs utilized in cosmetics are generally chemically synthesized, but there is an emerging shift towards green synthesis. Xia et al. demonstrated the use of ivy plant-derived NPs as an alternative to oxide particles in blocking UV rays (Bezbaruah et al., 2022).

Recently, NPs have been used for detection, diagnosis, and tumor therapy. NPs are excellent tools for cancer drug delivery because of their small size, which facilitates targeted delivery. NPs have also been used to mitigate adverse effects of photodynamic cancer therapy. The hydrophilic antigenic drug Mosqurix^® is used to treat malaria caused by Plasmodium falciparum and hepatitis B virus. This liposomal drug, modified as a phospholipid intrinsic adjuvant, has greater stability in the gastrointestinal tract for absorption. A nanogel made up of polyethylenimine along with cationic coated alginate, which is given intraperitonially, produces anti-ovalbumin IgG, which is promising for drug delivery (Adarsha et al., 2022). A dye used in photodynamic therapy migrates to the skin and eyes, leading to sensitivity. Partial encapsulation of the dye in NPs helped reduce sensitivity (Roy et al., 2003). Furthermore, NPs, such as gold NPs, have research applications, such as immunohistochemistry and identification of protein–protein interactions. Cao et al. (2003) synthesized a AuNP probe with catalytic activity for protein identification (Cao et al., 2003; Yadav et al., 2021). The extensive medical use of chemically made NPs has been reported to have adverse effects. Therefore, there has been a shift toward safer green synthetic bio-NPs. A study reported the use of nano-encapsulated AgNPs by green-synthesized pcDNA3.1/H5 for immunization through humoral and cell-mediated immune responses. Thus, green NPs can be used as an alternative DNA vaccine through nanotechnology for the oral administration of vaccines in a more effective way. AgNPs are an attractive and unique alternative delivery method for oral DNA vaccinations. NP-based vaccination showed a similar effect in the elucidation of the immune response as traditional vaccination procedures. In addition, it exhibits greater stability, cost-effectiveness, and target specificity in minimizing various disease types (Jazayeri et al., 2012).

Fungal based synthesized ZnNPs showed excellent antimicrobial property against pathogenic fish bacteria in comparison with chemical ZnNPs. This study also highlights the increase in immune response in organisms by the released Zn²⁺ hindering active transport as well as inhibiting bacterial enzymes in metabolism, leading to the release of ROS, causing death of the organism (El-Saadony et al., 2021). Similarly, biosynthesis of NPs from microbes and plant extracts has also shown vast application in modulating immune responses through innate and adaptive immunity across conditions, such as inflammation, cell differentiation and signaling during cancer, autoimmune disease, and allergic reactions. Hence, describing the ecofriendly and safer approach to green NPs is a novel therapeutic approach in drug delivery and therapeutics (Cai et al., 2022).

The size of the NP decreased from 30 to 3 nm, and the number of surface molecules increased from 10% to 50%. Metal NPs are the most common type of NPs employed in all industries. Studies on cellular uptake of gold NPs indicated their extracellular aggregation followed by enmass transport into the cells with resultant reactive species production and cytotoxicity ( Figure 5 ) (Goodman et al., 2004; Chithrani et al., 2006). Studies have shown that the formation of abnormal actin filaments results in decreased cell adhesion, proliferation, and motility (Pernodet et al., 2006). While gold nanospheres capped with citrate were non-toxic to baby hamster kidney and human hepatocellular liver carcinoma cells, they were toxic to human carcinoma lung cell lines at certain concentrations, signifying their effect on cell type (Pernodet et al., 2006).

Large concentrations of Ag in atmospheric air led to breathing abnormalities and lung, throat, and stomach discomforts. Ag n skin contact can occasionally lead to insignificant allergic conditions, such as rashes, swelling, and inflammation. However, several studies have been conducted (Carlson et al., 2008). However, studies have not proven the toxicity of spherical AgNPs and Ag nano-prisms in human skin keratinocytes. TiO₂ NPs induce oxidative stress by inducing changes in gene expression (Park et al., 2008). ZnO also induced toxicity by generating reactive oxygen species, oxidant injury, and inflammation, leading to cell death (El-Saadony et al., 2021).

In addition to humans, other animals and microbes such as zebra fish, daphnids, and algal species were exposed to silver, copper, aluminum, nickel, cobalt, and TiO₂ nanoparticles. Griffitt et al. (2008) detected toxicity levels in aquatic organisms owing to the presence of metallic NPs. In contrast, no toxicity was observed for TiO₂ NPs. These results were corroborated by another study on zebrafish embryos that suggested the dose-dependent developmental toxicity of Ag NPs (Asharani et al., 2008). The toxicity level of AgNPs in the aquatic environment can be denoted by the concentration accumulated by aquatic organisms. The liver is the initial accumulator organ for NPs in these aquatic organisms, followed by the gills, intestine, and muscles, causing cell necrosis and lysis in the intestinal villi, followed by progressive release of Ag ions (Liu et al., 2015). AgNPs are frequently used in apparel owing to their antimicrobial properties. However, the release of Ag, in both colloidal and ionic forms, from the fabric during washing causes its accumulation in the wastewater, leading to toxicity (Benn and Westerhoff, 2008).

ZnO NPs are readily used in cosmetics and, as such, are a large constituent of factory run off from the cosmetic industries. These NPs are toxic to Lolium perenne (ryegrass). ZnO-NP, along with the ryegrass biomass, has been able to suggestively reduce, characterized by shrinking the root tips, and highly vacuolated or collapsed epidermal or cortical cells (Lin and Xing, 2008). However, a minor reduction in root cells was detected upon exposure to uncoated alumina NPs (Yang and Watts, 2005).