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Antimicrobial nanoparticles: Present situation and future challenges
*Corresponding author: E-mail address: falkhataf@ksu.edu.sa (F. Alkhattaf)
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Received: ,
Accepted: ,
Abstract
The swift emergence of multidrug resistance across diverse microorganisms presents a major clinical obstacle for healthcare providers managing infectious diseases. In recent years, studies have concentrated on developing metal-based nanomaterials with antibacterial, antiviral, and antifungal capabilities to address contagious diseases. Various metal nanomaterials, including gold, copper, silver, palladium, and metal oxides like titanium, zinc, and iron, have shown promising antimicrobial effects against multidrug-resistant pathogens. The interaction between nanoparticles and biological systems is significantly affected by their physicochemical characteristics, such as size, shape, surface charge, ligand coating, doping, pH stability, surface roughness, and crystalline structure. Upon interaction, these nanoparticles exert their antimicrobial effects through multiple mechanisms, including increased production of intracellular reactive oxygen species, damage to cell membranes, disruption of membrane potential, DNA impairment, and destabilization of biofilms through interactions with their components. A comprehensive understanding of how specific physicochemical properties of metal nanoparticles relate to their antimicrobial mechanisms remains limited. Therefore, this review article examines key aspects of various nanoparticle types commonly applied in health and medical fields, with a focus on antimicrobial chemotherapy. It explores critical factors employed by nanoparticles to achieve antibacterial effects, as well as the antifungal, antibacterial, and antiviral mechanisms of metal nanoparticles.
Keywords
Antimicrobial
Metal-based nanoparticle
Metal oxide nanoparticles
Nanoparticles
Polymeric nanoparticles
1. Introduction
The World Health Organization has listed 12 emerging superbugs, resistant to multiple antibiotics, as priority targets for action, grouping them into critical, high, and medium priority categories. The absence of new drug discoveries, due to the extensive screening of natural resources, raises the risk of returning to a pre-antibiotic era. Governments acknowledge the pressing need for innovative approaches to address this global health challenge, fueled by progress in controlled nanoparticle technologies. These nanomaterials offer customizable biological properties for diverse biomedical uses, underscoring the critical need for new strategies to tackle antibiotic resistance (Nicolas et al., 2013).
Antibiotic resistance is globally acknowledged as a major public health threat. Research indicates that over 70% of bacterial infections can become resistant to primary antimicrobial agents used in clinical settings. Additionally, it is estimated that about 79% of bacteria develop resistance to one or more antibiotics. The consequences of antibiotic resistance extend beyond higher mortality and health risks, also driving up healthcare costs. Developing new antibiotics is a viable approach to combat this issue, but the process is time-consuming, often spanning years, which prevents rapid resolution of the immediate resistance problem. Moreover, this process is expensive, and new antibiotics remain effective only temporarily until resistance emerges again. This has economically constrained the development of new antibiotic classes (Salam et al., 2023). Consequently, there is an urgent need to develop effective antimicrobial agents. Nanoparticles have emerged as innovative tools to combat bacterial infections, offering potential solutions to overcome antibiotic resistance and the limitations of traditional antimicrobial treatments (Gupta et al., 2019).
2. Classification of antimicrobial nanomaterials
Based on their nanomaterial properties, antimicrobial nanoparticles can be classified into four main categories. Different types of antimicrobial nanomaterials (Fig. 1).
2.1 Metal-based nanoparticles
The antimicrobial efficacy of most metal-based coatings stems from their oligodynamic effect, which depends on ionic or nanoscale forms rather than bulk characteristics. The application of metals like gold, zinc, silver, and copper for antimicrobial purposes has been recorded since ancient times. These metals serve as antimicrobial agents capable of eliminating Gram-negative and Gram-positive bacteria, viruses, protozoa, and fungi. As a result, they have been utilized in antimicrobial products and medical applications for an extended period (Rai et al., 2009). Antibacterial surfaces should focus on inhibiting bacterial adhesion and growth. Various approaches can reduce or prevent bacterial colonization on biomaterial surfaces. Nevertheless, concerns persist about the development of antimicrobial resistance, and the potential toxicity risks associated with these surfaces remain significant (Mitwalli et al., 2020).
2.1.1 Silver nanoparticles (Ag NPs)
The techniques for Ag NPs production are numerous and encompass the physical techniques: 1) high-energy ball milling (Khayati et al., 2012), 2) arc-discharge (Elwakil et al., 2024), the chemical technique is a commonly employed technique of Ag NPs owing to its simplicity, versatility, and capacity to regulate nanoparticle size and morphology (Pinheiro et al., 2024), and biological techniques, of which the majority have emerged as an environmentally-friendly and more economical alternative in the domain of “green chemistry,” encompass plant-mediated biosynthesis (Ahmed et al., 2009). Ag NPs find application in wound care by promoting extensive collagen formation, thereby accelerating tissue repair while exhibiting anti-inflammatory properties (Ezhilarasu et al., 2020). The synthesized silver nanoparticles demonstrated significant antimicrobial efficacy when tested against both Gram-positive organisms, including Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis), and Gram-negative Escherichia coli (E. coli) bacteria. Gram-positive bacterial strains S. aureus and B. subtilis exhibited greater sensitivity to silver nanoparticles compared to Gram-negative E. coli (Li et al., 2013).
Ag NPs may contribute to the establishment of novel strategies for the enhancement of oral health and quality of life. Ag NPs have demonstrated to exhibit antiviral efficacy against HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV-inhibitory efficacy has not been completely elucidated (Monteiro et al., 2011).
According to the PubMed database alone, the antimicrobial properties of Ag NPs have been described in >1000 articles since 2015 till now (Fig. 2).
2.1.2 Gold nanoparticles (Au NPs)
Au NPs synthesis essentially pursues three different methods: physical methods, like pyrolysis (Weirich et al., 2020), chemical methods, like the Turkevich method (a classical method of Au NP synthesis) (Turkevich et al., 1951), and biological methods (Lee et al., 2015). Gold nanostructures may be engineered through various methods to achieve effective antimicrobial properties. These gold-based materials include nanospheres, nanotubes, clustered nanostructures, and core-shell particles. Enhancement of material properties can be achieved via coupling with additional compounds or by altering their structural configuration. Antimicrobial effectiveness may also be attained by linking gold nanoparticles with specific antibodies and diverse antimicrobial compounds. Au NP bound to antibiotics exhibit significant antimicrobial activity against multiple bacterial species and drug-resistant bacterial strains. Structure-function analysis of surface ligands on 2 nm gold nanoparticle cores demonstrated that antimicrobial characteristics of gold nanoparticles may be modified via surface hydrophobic properties, offering novel perspectives for antimicrobial nanomaterial development (Li et al., 2014). The benefits of AuNPs as antibacterial agents are as follows: (1) Gold nanomaterials can achieve high biosafety due to gold’s chemical inertness, with their absorption and metabolism controlled through material design. (2) The antibacterial properties of AuNPs can be optimized by chemically adjusting characteristics like size, shape, and surface through surface modification with various molecules. (3) Gold nanomaterials are less likely to cause bacterial resistance compared to conventional antibiotics (Zhao et al., 2022).
According to the PubMed database alone, the antimicrobial properties of Au NPs have been described in >1000 articles since 2015 till now (Fig. 3).
2.1.3 Copper nanoparticles (Cu NPs)
The production of Cu NPs involves a varied spectrum of techniques that facilitate generating nanoparticles. These methods fall into three main methods: physical methods: 1) Deposition of physical vapor (Krishnia et al., 2022), Chemical methods: sol-gel (Bokov et al., 2021), green methods: bacterial biosynthesis (Gebrie et al., 2025), fungal biosynthesis (Salem et al., 2021). The antimicrobial efficacy of Cu NPs is equivalent to that of Ag NPs, but they demonstrate reduced effectiveness against Gram-negative strains. Comparable to other metal NPs, tinier dimensions display superior bactericidal impact, owing to increased surface/volume proportion and closer interaction with membrane and bacterial wall structures. Cu NPs, incorporated in dendritic polyglycerol, have been discovered to demonstrate elevated antibacterial efficacy against both Gram-negative and Gram-positive strains, plus antibiotic-resistant ones (Li et al., 2017). The antibacterial mechanism incorporates an “attract-kill-release” procedure through reactive oxygen species (ROS) production and Cu2+ release, displaying extended biocompatibility characteristics. Cu NPs can harm the bacterial cell membrane and penetrate cells to disturb enzyme function, resulting in bacterial death. Cu NPs provide reduced production expenses relative to other metal nanoparticles, like Ag NPs and Au NPs. This combination of reduced production expenses and green technology has yielded elevated antimicrobial and anticancer characteristics, minimizing cytotoxic side effects (Yoosefi et al., 2015).
According to the PubMed database alone, the antimicrobial properties of Cu NPs have been described in >400 articles since 2015 till now (Fig. 4).
2.2 Metal oxide nanoparticles
Metal oxide nanoparticles are nanometer-scale particles composed of metallic and oxygen atoms, creating metal-oxygen complexes. They possess distinctive physical and chemical characteristics owing to their minute dimensions and elevated surface area, and are manufactured from transition metals such as iron, copper, titanium, and non-metals such as silicon and aluminium.
2.2.1 Zinc oxide nanomaterials (ZnO NPs)
All methods used for synthesizing Zn NPs could be applied with ZnO NPs. Inorganic antimicrobial compounds provide benefits like selectivity, toxicity, resistance, and stability relative to organic alternatives. Zinc oxide (ZnO) is especially beneficial owing to its elevated thermal resistance, selectivity, cytotoxicity, and stability. Nanoparticles (NPs) possess enhanced characteristics relative to bulk materials, improving cellular interactions and maximizing antimicrobial efficacy through increased contact surface area (Da Silva et al., 2019). Antimicrobial efficacy of ZnO NPs against the clinically important bacteria E. coli, S. aureus, Pseudomonas aeruginosa, and the Gram-positive model B. subtilis was assessed. The findings demonstrated that 70% of the cells displayed injury in the cytoplasmic membrane following 15 min of contact with the ZnO NPs (Mendes et al., 2022). ZnO NPs are multi-target agents that impact various bacterial cell structures, including cell morphology and DNA, and compromise the cell membrane. Their primary mechanism of action targets the cytoplasmic membrane, with other structural damages occurring as secondary effects following membrane disruption. ZnO NPs have powerful antifungal properties against Fusarium equiseti (Subba et al., 2024).
According to the PubMed database alone, the antimicrobial properties of ZnO NPs have been described in >500 articles since 2015 till now (Fig. 5).
2.2.2 Copper oxide nanomaterials (CuO NPs)
The synthesis of CuO NPs has been accomplished through various physical, chemical, and green methods. Cu is a highly conductive substance and is more economical than materials like gold (Au) and silver (Ag). Since CuO phases are more thermodynamically stable than pure copper, most of the produced CuO NPs possess surface oxide coatings. The widely accepted antimicrobial action mechanism of copper-based nanomaterials relies on the liberation of Cu2⁺ ions. Copper ions can harm the bacterial cell membrane and penetrate cells to disturb enzyme function, resulting in bacterial death (Saleem et al., 2025).
CuO NPs possess substantial bacteriostatic capacity regarding a broad spectrum of microorganisms. Based on certain authors, the more distinct antimicrobial effect of CuO NPs against Gram-positive bacteria like S. aureus and B. cereus is notable (Tiwari et al., 2014).
According to the PubMed database alone, the antimicrobial properties of CuO NPs have been described in >2000 articles since 2015 till now (Fig. 6).
2.2.3 Titanium dioxide nanoparticles (TiO₂ NPs)
Conventional methods for synthesizing TiO₂ NPs can be classified into three categories: physical, chemical, and green methods (Chandoliya et al., 2024). The study of TiO2 surface and its applications in nanomedicine and nanobiotechnology has been extensive, with TiO2 being highly attractive for bactericidal activity due to its chemical stability, natural abundance, and low cost (Liao et al., 2020).
The antimicrobial properties of TiO2 NPs against a considerably broad spectrum of microorganisms with epidemiological importance are documented, encompassing Gram-positive (Gr+) (B. subtilis) (Morozova et al., 2024), there are developing findings regarding the antiviral efficacy of TiO2 NPs, specifically against H3N2 influenza virus (Schutte-Smith et al., 2023).
According to the PubMed database alone, the antimicrobial properties of TiO₂ NPs have been described in >200 articles since 2015 till now (Fig. 7).
2.2.4 Iron oxide nanoparticles (IO NPs)
The methods for IO NPs synthesis are multiple and include the chemical method (Prabhu et al., 2015), and green synthesis (Priya et al., 2021). IO NPs have insignificant antimicrobial activity against Gr- such as E. coli and Klebsiella pneumoniae (Vasantharaj et al., 2019). Nevertheless, research on IO NPs has garnered minimal focus as prospective antiviral agents. Artificially produced IONPs demonstrated antiviral efficacy against H1N1 Influenza A virus (Kumar et al., 2019).
According to the PubMed database alone, the antimicrobial properties of IO NPs have been described in >600 articles since 2015 till now (Fig. 8).
2.3 Antimicrobial polymeric nanoparticles
Presently, multidrug-resistant bacterial infections are increasing, encouraging scientists to investigate novel antimicrobial compounds, including polymeric nanostructures. Progress in controlled polymerization methodologies has resulted in examining these nanostructures as prospective therapeutic agents to address escalating infectious disease prevalence. Synthetic polymers can demonstrate inherent antimicrobial properties by replicating naturally-occurring adenosine monophosphate (AMP) chemical compositions. These polymers integrate cationic and hydrophobic segments, enabling interaction with negatively charged bacterial cellular walls and promoting microbial membrane infiltration (Liu et al., 2012). Nevertheless, antimicrobial polymers featuring alternative chemical compositions, including quaternary ammonium-based polymers lacking hydrophobic elements, have been documented. Antimicrobial activity enhancement through nanostructure formation draws inspiration from biological multivalent interactions, where concurrent binding of multiple ligands to multiple receptors can produce amplified effects (Mammen et al., 1998).
Wang and colleagues’ 2009 and 2010 studies demonstrated This hypothesis was substantiated by the fact that core-shell micellar nanoparticles, made from an amphiphilic peptide, demonstrated superior antimicrobial properties against various Gram-positive bacterial and fungal species. This occurred because of enhanced positive charge concentration and peptide molecular weight, leading to more robust electrostatic binding with negatively charged bacterial membranes (Wang et al., 2012).
This portion will explore synthetic polymer-based nanoarchitectures (mainly produced via regulated polymerization techniques) that demonstrate inherent antimicrobial properties. These polymer nanostructures are categorized based on their complex molecular arrangements, alongside the effects of such polymeric designs on antimicrobial performance. According to the PubMed database alone, the antimicrobial properties of polymer NPs have been described in >2500 articles since 2015 till now (Fig. 9).
3. Antimicrobial nanomaterials mechanisms
The comprehensive antimicrobial pathways of various nanoparticle categories remain incompletely elucidated. Therefore, it becomes essential to decipher the mechanistic routes through which these materials exhibit biocidal properties in order to develop nano-formulations incorporating nanomaterials as wide-spectrum, effective antimicrobial agents. In this study, we examine antifungal, antibacterial, and antiviral mechanisms employed by antimicrobial nanomaterials.
3.1 The antifungal mechanisms of nanomaterials
Mechanisms of antifungal activity of nanoparticles (Fig. 10).
3.1.1 Membrane damage
The NPs can induce fungal cellular wall alterations, including surface contraction, cellular clustering, cavity and aperture development, and structural distortion. Microscopic examination reveals NPs may establish direct contact and integration within cellular walls during adsorption, producing morphological modifications. Internal membranes also experience distortion, with modified organelle arrangement (Lara et al., 2015).
Alternative nanocomposites, including MgO/CuO NPs combined with antifungal nystatin, demonstrated that C. albicans exposure resulted in cellular membrane damage and intracellular component leakage. Following 24 hours, 94% of organisms reached advanced apoptotic phases, with proteins and DNA escaping through compromised cellular walls (Martínez et al., 2021). Ag NPs caused substantial cellular wall damage in yeast organisms. The cytoplasmic membrane became separated from the cellular wall, and organelles exhibited swelling. Additionally, yeast organisms underwent enlargement and experienced cytoplasmic leakage with cellular wall compromise, though most organisms maintained their morphology and cellular wall structure (Hwang et al., 2012).
3.1.2 DNA interactions
Ag NPs caused DNA condensation and fragmentation in C. albicans nuclei, suggesting that oxidative stress and DNA damage can be influenced by Ag ions binding to negatively charged DNA. The direct damage, including nuclear condensation and fragmentation, could lead to cellular dysfunction and apoptosis DNA fragmentation within the nucleus requires NPs to traverse nuclear membranes or generate substantial intracellular membrane damage for DNA contact. Furthermore, ions liberated from NPs may influence nuclear membrane integrity (Pradhan et al., 2015).
3.1.3 Ion release
Ionic liberation has demonstrated enhanced antimicrobial effectiveness over time, with certain investigations indicating that ions exhibit greater toxicity than NPs owing to their dimensions and capacity to coordinate with additional biomolecules. Thiol molecules function significantly in detoxification within arsenic-resistant Aspergillus ssp., and ionic release may disrupt fungal detoxification mechanisms. Cytoplasmic ions remain vital for sustaining reducing environments. ROS generated by ions liberated from NPs under oxidative conditions could deplete thiol concentrations, modifying intracellular redox balance and potentially triggering apoptotic pathways (Chen et al., 2020).
3.1.4 Damage to hyphae and spores
NPs can produce severe effects on fungal hyphae and spores. Fungi exposed to Ag NPs, MgO NPs, ZnO NPs, or CuNPs exhibited hyphal structural alterations, appearing deformed and contracted. NPs modify proliferation patterns, causing hyphal fiber clustering and attenuation (Chen et al., 2016). SiO₂ NPs achieved mycelial radial growth reduction up to 100% at 100 μg/mL concentrations. These demonstrated dose-responsive behavior, affecting mycelium fresh and dry mass. NPs’ antifungal effectiveness results from their impact on spores and germination processes, potentially causing hyphal structural abnormalities (Westmeier et al., 2018).
Multiple hypotheses exist regarding NP effects on spores and formulation-dependent factors. Spore surfaces possess negative charges attributed to hydrophobins, which are low molecular weight proteins. Polymer nanoparticles (PNP) with comparable dimensions bind more effectively than positively charged variants, and enhanced positive charge fails to improve attachment or adsorption. This pattern continues in ion-depleted buffers, eliminating potential ionic influences (Aslani et al., 2018).
3.1.5 Effect on biofilm formation
Fungal biofilms comprise sessile cellular communities attached to surfaces. Fungal organisms capable of biofilm development exhibit increased resistance within their biofilm configuration. Extracellular polymeric substance (EPS) production, elevated resistance gene expression, and altered proliferation rates contribute to pathogenicity and therapeutic tolerance. Biofilms represent a major clinical challenge, particularly in C. albicans, a fungal organism capable of generating mature biofilms with enhanced structural stability, yet these formations are not morphology-dependent and can establish within yeast and hyphal cells, contrasting with other organisms such as S. cerevisiae (Harrison et al., 2006).
Candida biofilm matrices possess the ability to bind metallic cations from different metal compounds onto the extracellular matrix, thereby conferring protective mechanisms. These biofilm communities exhibit 65-fold greater resistance to metallic toxicity compared to free-floating cell populations, with copper and nickel ions creating metal-binding complexes on the extracellular matrix, indicating that absorption mechanisms contribute to stress tolerance (Pócsi et al., 2004).
3.1.6 ROS generation
ROS constitute a group of oxidizing agents typically produced during metabolic processes and include compounds like hydrogen peroxide, superoxide anions, and hydroxyl radicals. Under adverse environmental circumstances, mammalian cells synthesize elevated levels of ROS, resulting in cellular damage that eventually leads to growth inhibition or cellular demise. Glutathione represents a sulfur-containing compound in yeast and filamentous fungi essential for cellular function and stress management. Glutathione exhibits antioxidant properties and interacts with ROS to protect cellular structures. Glutathione polymers called “phytochelatins” play crucial roles in fungal heavy metal detoxification by capturing metal ions or through ROS production (Kalagatur et al., 2018).
The research employed nitro blue tetrazolium reduction methodology to identify superoxide radicals within Alternaria brassicicola, demonstrating formazan accumulation in fungal mycelial structures treated with silver nanoparticles [51]. Reduced membrane permeability results in intracellular reactive oxygen species formation. The elevation in lipid peroxidation is theorized to result from ROS generation, since this represents an established mechanism (Di Meo et al., 2016).
3.1.7 Gene regulation and protein levels
Nanoparticle treatment may modify genetic expression and protein concentrations, possibly providing antifungal resistance in fungal organisms, since such modifications are anticipated following contact with substances possessing antimycotic properties.
The research investigated metal contamination effects on enzyme concentrations across five fungal isolates from waterways under conditions without and with CuO nanoparticle treatment. Findings indicated that unpolluted fungi exhibited elevated glutathione peroxidase (GPX) and reduced GR function, resulting in diminished reduced glutathione (GSH) concentrations. Contaminated fungi sustained elevated GSH concentrations. superoxide dismutase (SOD) function rose following CuO NP treatment, with greater concentrations observed in metal-contaminated fungi. Consequently, metal acclimatization in fungi may develop tolerance strategies, primarily managing oxidative damage, which can extend to withstanding nanoparticle treatment (Dakal et al., 2016).
3.2 The antibacterial mechanisms of nanomaterials
This section examines antibacterial mechanisms of metallic nanoparticles encompassing (i) bacterial cell wall attraction and metallic nanoparticles through contrasting surface charges and membrane destabilization; (ii) ROS generation; (iii) metallic ion release; and (iv) signaling pathway alterations. Mechanisms of antibacterial activity of nanoparticles (Fig. 11).
3.2.1 Interaction with cellular (cell wall and membrane) compartments
Metal-based nanoparticles possessing positive surface charges bind to bacterial cell walls and membranes through their negative surface charges. Negatively charged cellular membranes and nanoparticles experience electrostatic attraction, facilitating adhesion processes. Similar patterns occurred when positively charged magnetic nanoparticles (NP+) attached to approximately 90% of E. coli cells. This subsequently affects cellular membrane permeability enhancement and lipid bilayer structural integrity. Increased membrane permeability may produce more serious consequences beyond compromised transport mechanisms, including cellular content loss through leakage, such as ions, proteins, reducing sugars, and occasionally adenosine triphosphate, the cellular energy storage molecule (Singh et al., 2013).
3.2.2 Binding to proteins
Metallic NPs can exhibit antibacterial properties through protein dysfunction and enzyme inactivation. Ag+, for instance, can denaturate and inhibit protein and enzyme synthesis for ATP production by oxidizing amino acid side chains, demonstrating various antibacterial mechanisms. Ag NPs and Ag (+) ions interact with proteins, modifying their three-dimensional architecture, disrupting disulfide bonds, and obstructing binding sites. This produces functional complications in microorganisms, suppressing protein phosphorylation, enzymatic activity, and bacterial proliferation. NP advantages include cellular protein inactivation, DNA damage, and metabolic enzyme disruption (Maji et al., 2020).
3.2.3 Formation of reactive oxygen species
Metal-based nanoparticles penetrate bacterial cells, deactivate respiratory enzymes, and enhance free radical generation, including H2O2, O2•−, and HO•, resulting in bacterial mortality. Nanoparticles’ high oxidation potential can cause damage to biomolecules and organelle structures, including protein oxidative carbonylation, lipid peroxidation, DNA/RNA breakage, enzyme inhibition, and membrane structure destruction. Furthermore, reactive oxygen species enhance oxidative protein gene expression levels, representing a fundamental mechanism in bacterial cellular apoptosis processes (Radzig et al., 2013).
3.2.4 Interaction with DNA
Metallic nanoparticles cause genomic alterations in microbial cells, leading to the condensation of genetic materials, suppressing essential cellular functions, ultimately causing cell necrosis and death. Specifically, hydroxyl radicals (OH•), among the strongest oxidizing species, interact with all DNA constituents, producing single-strand cleavage through 8-OHdG-DNA adduct formation mechanisms. In E. coli, silver nanoparticles cause genetic material damage (including strand fragmentation) and alterations in essential DNA repair genes or chromosomal abnormalities and oxidative nucleotide base deterioration (Rodrigues et al., 2021).
3.3 The antiviral mechanisms of nanomaterials
These nanoparticles have demonstrated effectiveness against diverse viruses, including SARS-CoV-2, HIV, herpes simplex virus (HSV), influenza (H1N1), hepatitis B (HBV), hepatitis C (HCV), Ebola, poliovirus, and others. These mechanisms encompassed (1) direct nanoparticle-virus interaction, functioning as virucidal agents (2) nanoparticle-receptor interaction, preventing viral cellular entry; (3) nanoparticle cellular infiltration disrupting viral assembly and processing; or (4) nanoparticle inhibition of viral replication. Mechanisms of antiviral activity of nanoparticles (Fig. 12).
3.3.1 Nanoparticles direct interaction with the virus
Antiviral mechanisms against viruses can operate intracellularly (therapeutic) or extracellularly (preventive). Extracellular prevention approaches involve nanoscale viral interactions, including virucidal effects, viral binding, receptor blocking, and nanoparticle antiviral delivery. These approaches prevent fusion, entry, and infectivity, deactivate viruses, and obstruct host cell receptors (Zhou et al., 2021). Nanomaterials including metal nanoparticles and graphene-derived nanosheets possess inherent virucidal properties attributed to their distinctive physicochemical characteristics. They interact with viral envelope or capsid proteins, compromising structural integrity and suppressing infectivity. Ag NPs obstruct virion entry and replication, whereas copper nanoparticles and composites produce ROS and oxidize capsid proteins, suppressing swine H1N1 influenza virus (Lin et al., 2021).
3.3.2 Nanoparticles interaction to receptors, blocking viral entry inside the cells
Antiviral nanoparticles interact with host cells to prevent virus entry by blocking receptor sites or altering virus structure, preventing proper attachment to the receptor. Viruses infiltrate host cells via specific membrane receptors, utilizing attachment proteins within viral capsids or envelope glycoproteins. The interaction mechanism determines host cell types that viruses infect. Bacteriophages infiltrate by maintaining capsids outside cells while permitting nucleic acid entry. Animal and plant viruses enter through endocytic processes. RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), synthesize viral genomic RNA and release new virions (Nefedova et al., 2022).
3.3.3 Preventing the production of virion components
Research evaluated two cerium oxide (CeO2) nanoparticles possessing contrasting surface charges, positive (+) and negative (−), regarding their potential to reduce viral component synthesis in coronavirus SARS-CoV-2 and influenza (enveloped pathogens). Significant suppression of component biosynthesis and antiviral efficacy against enveloped coronavirus SARS-CoV-2 and influenza pathogens occurred at concentrations of 20 mg Ce/l. CeO2 demonstrates substantial nucleic acid affinity in adeno-associated virus, adenovirus, human immunodeficiency virus, and murine leukemia virus, interacting with genetic materials following protective capsid dissolution during intracellular replication processes (Milovanovic et al., 2017).
4. Conclusions
Throughout the previous two decades, increasing attention has focused on antibacterial nanomaterial investigation, with this analysis highlighting their microbial cellular interactions and impacts. However, these nanoparticles’ biomedical applications remain restricted due to their nonselective biomolecular reactivity. Recently, researchers have studied nanomaterial antimicrobial effectiveness against eukaryotic and prokaryotic organisms. Multiple organic and inorganic compounds have been utilized to alter nanomaterial activity effectiveness and scope. Nevertheless, our comprehension of molecular-level nanomaterial action modes in planktonic and biofilm-producing microorganisms remains constrained. Additionally, comprehensive antimicrobial pathways of various nanoparticle types remain incompletely elucidated. Therefore, it becomes essential to decipher mechanistic routes of biocidal and antibiofilm activities in these materials to develop nano-formulations incorporating nanomaterials as wide-spectrum, effective antimicrobial agents. Although antimicrobial nanoparticles show potential for diverse uses, their safe and efficient application requires addressing multiple obstacles. Key challenges include: Emergence of resistance: Prolonged and widespread use of antimicrobial nanoparticles may lead to microbial resistance. Research is needed to understand resistance mechanisms and develop countermeasures, Toxicity and Biocompatibility: Assessing the long-term safety and toxicity of antimicrobial nanoparticles is vital. Their impact on human health and ecosystems must be thoroughly evaluated for safe use, Ecological Consequences: The intentional or unintentional release of antimicrobial nanoparticles into the environment raises concerns about their effects on ecosystems, aquatic life, and soil health. Studying their dispersion, behavior, and ecological impact is critical, Impact on Beneficial Microbiota: Antimicrobial nanoparticles may harm not only pathogens but also beneficial microbial communities. Maintaining microbial balance is crucial for overall health, Formulation Refinement: Optimizing nanoparticle properties, such as size, shape, surface charge, and coatings, is necessary to enhance effectiveness while minimizing negative effects, Targeted Delivery Issues: Delivering antimicrobial nanoparticles to specific body sites remains difficult. Developing systems for controlled release and precise localization is essential, Regulatory Oversight: Creating robust regulatory guidelines for the approval and monitoring of antimicrobial nanoparticles is critical to ensure safety and efficacy across applications, including testing protocols. Proper disposal methods should be established, treating them as potential biohazards. Bodies worldwide actively assess nanomaterial safety, Targeted Bacterial Engineering: Nanoparticles can be designed to selectively target bacterial cells. When concentrated at infection sites, applying near-infrared light induces localized heating, damaging nearby bacteria, which requires further optimization, Combined Photothermal and Photodynamic Therapies: Integrating photothermal therapy (PTT) with photodynamic therapy (PDT) can yield synergistic effects. Heat from PTT can enhance photosensitizer performance in PDT, boosting reactive oxygen species production. This combination may offer unique antimicrobial properties with improved selectivity and fewer side effects, Preventing Gene Transfer: Nanoparticles can be engineered to block the spread of antibiotic resistance genes among bacteria, limiting resistance proliferation within microbial populations, Minimizing Immune Detection: Surface modifications can reduce immune system recognition of nanoparticles, extending their circulation time and improving therapeutic outcomes.
Acknowledgement
The authors extend their appreciation to the Researchers supporting project number (ORF-2026-224) King Saud University, Riyadh, Saudi Arabia.
CRediT authorship contribution statement
Fatimah S. Al-khattaf: Writing – original draft, Methodology, Investigation, Data curation, Conceptualization, Visualization, Validation, Methodology, Visualization, Validation, Supervision, Supervision, review and editing, Writing – original draft, Conceptualization, Supervision, Resources, Project administration, and Funding.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data availability
The data used to support the findings of this study are all in the manuscript.
Declaration of generative AI and AI-assisted technologies in the writing process
The authors confirm that there was no use of Artificial Intelligence (AI)-Assisted Technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Funding
This research project was funded by the Researchers supporting Project number (ORF-2026-224) of King Saud University, Riyadh, Saudi Arabia.
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