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Metal Nanomaterials: A Strategy to Combat Drug-Resistant Bacterial Infections
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Yaran Wang1, 2, Fan Wu1, 2, Yijin Ren3, *, Yong Liu1, *, Henny C. van der Mei2, *
Research. Vol 8 Article ID 0853
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Research. Vol 8 Article ID 0853
• Perspective •
Metal Nanomaterials: A Strategy to Combat Drug-Resistant Bacterial Infections
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Yaran Wang1, 2, Fan Wu1, 2, Yijin Ren3, *, Yong Liu1, *, Henny C. van der Mei2, *
Affiliations
  • 1State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
  • 2Department of Biomaterials and Biomedical Technology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
  • 3Department of Orthodontics, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
About Author:

† These authors contributed equally to this work.

Published: 2025-08-20 doi: 10.34133/research.0853
Outline
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Bacterial infections pose a major challenge today due to the rise of drug resistance in pathogenic bacteria, creating an urgent need for the development of nonantibiotic therapies. Metal nanomaterials are increasingly recognized as promising antibacterial agents due to their unique physical and chemical properties, which offer strong antibacterial capabilities and broad-spectrum activity against drug-resistant bacteria. Unlike traditional antibacterial therapies, metal nanomaterials rarely induce drug resistance because of their diverse antibacterial mechanisms, which destroy bacteria by directly damaging bacterial cells or generating oxidative stress. Metal nanomaterials have proven effective in treating various drug-resistant bacterial infections. This perspective highlights recent advances in metal nanomaterials for antimicrobial applications. Firstly, bacterial infections and the current dilemma are introduced. Next, recent progress in the antibacterial activity of metal nanomaterials against drug-resistant bacteria is summarized, along with the challenges in their antimicrobial applications. Finally, future prospects and remaining challenges associated with the use of metal nanomaterials to treat drug-resistant bacteria are discussed.

Yaran Wang, Fan Wu, Yijin Ren, Yong Liu, Henny C. van der Mei. Metal Nanomaterials: A Strategy to Combat Drug-Resistant Bacterial Infections[J]. Research, 2025 , 8 (8) : 0853 - . DOI: 10.34133/research.0853
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Bacterial Infections: The Current Antibiotic Dilemma
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Bacterial infections have emerged as a global challenge and a major threat to human health. Since the discovery of antibiotics, previously fatal bacterial infections have been largely controlled. However, excessive antibiotic use and microbial evolution have led to antibiotic resistance [1,2]. Microorganisms acquire resistance mainly through genetic mutations that alter antibiotic binding sites, reducing target affinity and decreasing effectiveness. Additionally, resistance mechanisms such as enzymatic inactivation, efflux pumps, alternative metabolic pathways, and altered permeability have further reduced antibiotic efficacy [3,4]. Biofilm formation worsens this problem, as bacteria in biofilms are protected from antibiotics and the immune system by the extracellular matrix. This makes it hard for drugs to penetrate and kill the bacteria [5]. As a result, antibiotic therapy has become less effective against drug-resistant infections. There is now an urgent need for novel, effective nonantibiotic strategies to combat drug-resistant bacteria.
Antibacterial Activity of Metal Nanomaterials
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Nanomaterials are considered a promising alternative to antibiotics due to their low cost, convenient synthesis methods, biocompatibility, environmental friendliness, and broad applicability [6]. Among these, metal nanomaterials are currently one of the fastest developing and most widely used, owing to their long history in antibacterial applications, such as the traditional use of gold and silverware before the advent of antibiotics [7]. Their nanoscale size and high surface-to-volume ratio enable superior physical and chemical properties and antibacterial activity compared to bulk metal materials. To date, metal nanomaterials have been developed in various formulations, including pure metals, alloys, metal oxides, metal sulfides, and metal-organic frameworks, with applications in drug delivery and antimicrobial therapy.
Unlike traditional antibiotics that act on specific molecular targets (a key driver of antimicrobial resistance), metal nanomaterials exert multifaceted, nonspecific antibacterial mechanisms, such as membrane disruption and reactive oxygen species (ROS) generation [8–10]. These nontargeted modes of action reduce the potential for resistance development and provide broader-spectrum antimicrobial activity compared to antibiotics (Figure 1) [11]. Other nanomaterials like carbon-based and organic nanomaterials such as graphene oxide are interacting and disrupting cell membranes and can produce ROS with photodynamics but have a disadvantage: they have only a few mechanisms to kill multidrug-resistant bacteria.
Furthermore, metal nanomaterials demonstrate high efficacy against biofilms due to their nonspecific targeting and penetration capabilities. Table 1 provides a comprehensive overview of various metal nanomaterials, highlighting their different antibacterial mechanism to overcome bacterial infections. One of the primary mechanisms involves ROS generation, in which metal nanomaterials such as Ag nanoparticles and ZnO nanoparticles induce oxidative stress and cause bacterial cell damage. This mechanism is especially effective against drug-resistant bacteria, as ROS can target various bacterial biomolecules, thereby reducing the likelihood of resistance development [12]. Moreover, metal nanomaterials are capable of bypassing bacterial resistance mechanisms through modulation of bacterial membrane efflux and permeability, release of heavy metal ions, excitation of phototherapy, and effective prevention of biofilm formation, thereby enhancing their antimicrobial efficacy [13]. This makes them promising candidates in the ongoing battle against drug-resistant pathogens.
Challenges in Antibacterial Applications of Metal Nanomaterials
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The evolution of bacterial resistance to metal nanomaterials is still in its early stages. Effective resistance prevention requires multiple antibacterial mechanisms. Emerging evidence suggests that prolonged use of metal nanomaterials may induce resistance. For instance, Escherichia coli and Pseudomonas aeruginosa treated with Ag nanoparticles have exhibited resistance through phenotypic changes, including enhanced flagellar assembly that promotes Ag aggregation [14]. Therefore, synergistic approaches combining metal nanomaterials with other antibacterial strategies, such as photothermal therapy, chemodynamic therapy, or photodynamic therapies, hold great promise. These approaches offer enhanced efficacy while reducing resistance risks.
The biosafety of metal nanomaterials represents a major barrier to clinical translation. Unlike traditional medicines, they may induce oxidative stress, inflammation, and cellular damage [15,16]. Their cytotoxicity strongly depends on physicochemical properties, including size, shape, surface charge, composition, and solubility. For instance, positively charged metal nanomaterials penetrate cell membranes more readily and interact with intracellular organelles than negatively charged ones [17]. Several methods have been employed to improve biosafety, including biosynthesis, surface modification with natural compounds, and hybridization with other nanomaterials to reduce metal concentrations while maintaining activity [18]. It is important to avoid the accumulation of metal nanomaterials in the human body; therefore, biodegradation and metabolism also need to be studied. The distribution and clearance of metal nanomaterials can be tracked by labeling with radiotracers in animal and human studies. Furthermore, the presence of metal ions in biological samples (e.g., blood, urine, and tissues) needs to be monitored.
Most applications of metal nanomaterials remain preclinical, with animal studies dominating current research. In vivo evaluations using various infection models, ranging from wound healing and oral infections to systemic conditions like peritonitis, have provided valuable therapeutic insights [19]. While some metal nanomaterials, including Au-, Ag-, Cu-, Zn-, Ti-, and Fe-based nanomaterials, have been used in clinical trials, their current applications focus primarily on diagnostics rather than infection treatment. For example, Au (NCT04907422) is being used as a biomarker, Fe (NCT00920023) is used for tumor imaging, and Cu (NCT04334837) is used for tumor detection. These examples demonstrate their clinical potential while emphasizing the need for further optimization and comprehensive clinical evaluation to advance infection applications from laboratory research to clinical trials and ultimately to market approval. The translational imperative hinges on establishing robust preclinical validation and iterative clinical feedback. Firstly, a thorough evaluation of the safety profiles of metal nanomaterials in vivo is essential, including prolonged toxicity, biodistribution, and metabolic pathways. Then, extensive clinical datasets derived from diverse human populations are essential. This involves integrating rigorous preclinical validation with human data feedback, driven by synergistic partnerships between academia, industry, and the regulatory sector.
Conclusions and Future Prospects
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Over the past 5 years, nearly 9,000 papers (according to Web of Science, keywords: “metal nanomaterial” and “antibacterial”; assessment date: May 2025) have been published on metal nanomaterials for antibacterial infections. However, the rapid growth in research has far outpaced practical applications, with most advancements remaining confined to laboratory settings. Therefore, further efforts should prioritize multidisciplinary in-depth research, including studies on drug-resistance mechanisms, long-term biosafety, and clinical trials, rather than on developing more new metal nanomaterials. To effectively prevent antibacterial resistance, the underlying mechanism must be fully understood through comprehensive long-term in vitro and in vivo studies. Since most bacterial infections involve multiple species, in vitro studies should use mixed species biofilms to better reflect clinical conditions. Finally, for successful clinical translation, the production process must meet 3 key criteria: high quality standards, scalability, and cost-effectiveness.
Funding
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  • National Natural Science Foundation of China(52444307)
  • UMCG
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Appendix
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Year 2025 volume 8 Issue 8
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Article Info
doi: 10.34133/research.0853
  • Receive Date：2025-06-12
  • Online Date：2026-11-01
  • Published：2025-08-20
Article Data
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History
  • Received：2025-06-12
  • Revised：2025-07-31
  • Accepted：2025-07-31
Funding
National Natural Science Foundation of China(52444307)
UMCG
Affiliations
    1State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
    2Department of Biomaterials and Biomedical Technology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
    3Department of Orthodontics, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.

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* Address correspondence to: (H.C.v.d.M.);
, (Y.L.);
(Y.R.)
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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