Antimicrobial Nanomaterials: History
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Gaye Ezgi Yılmaz
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Ilgım Göktürk
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Mamajan Ovezova
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Fatma Yılmaz
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Adil Denizli

Incorporating antimicrobial nanocompounds into materials to prevent microbial adhesion or kill microorganisms has become an increasingly challenging strategy. Many studies have been conducted on the preparation of nanomaterials with antimicrobial properties against diseases caused by pathogens. 

  • antibacterial
  • nanomaterial
  • metalic nanoparticles

1. Introduction

The developing technology in the field of antimicrobial coating can make an important contribution to overcoming biofilms in various fields, such as food, medicine, and agriculture. Biofilm-associated infections cause serious public health burdens and major economic losses [1]. Pathogenic infectious agents that form biofilms remain alive on surfaces for a long time. It is also known that multi-drug-resistant bacterial strains can survive for weeks on different surfaces in the hospital [2]. The National Institute of Health announced that biofilms are responsible for 80% of the total number of microbial infections in humans [3], including meningitis, cystic fibrosis, kidney infections, endocarditis, rhinosinusitis, periodontitis, non-healing chronic wounds, osteomyelitis, prosthetic, and implantable medical device infections [4].
The main difficulties in the treatment of biofilms are that they are difficult to remove in the clinic and are not easy to diagnose due to their high tolerance to antibiotics [5]. Numerous molecules that inhibit biofilm formation or disperse the resulting biofilms have been identified. Nanoparticles, antibiotics, antimicrobial peptides, enzymes, quaternary ammonium compounds, superhydrophobic coatings, and anti-adhesive polymers are used as antimicrobial strategy types in surface coatings [6][7][8]. With the latest developments in nanotechnology, new opportunities for effective biofilm treatment and control have become the focus of attention. Nanotechnology-based strategies allow the fabrication of nanoscale surfaces that can both reduce bacterial adhesion and increase osseointegration without the use of biomolecules or antibiotics, as well as the promise of biomaterials and medical devices to prevent drug-resistant biofilm infections [9]. Because NPs are very small in size, they cause irreversible damage to DNA and cell membranes by penetrating microbial cell walls and even biofilm layers. In addition, these structures have long plasma half-lives and facilitate drug loading and the targeting of entities due to their high surface-to-volume ratio [10]. The antibacterial activity of most metal-based coatings is attributed to their oligodynamic effect, which is ionic or nanoform dependent, as opposed to bulk properties. The use of metals such as gold, zinc, silver, and copper for various antimicrobial purposes has been documented since ancient times. These substances are antimicrobial agents that have the power to kill Gram-negative and Gram-positive bacteria, viruses, protozoa, and fungi. Therefore, these substances have been used in antimicrobial-based products and the field of medicine for a long time [11][12]. Antimicrobial surfaces should aim to prevent bacteria colonization and attachment [13]. Different strategies can limit or prevent bacterial colonization on the biomaterial surface. However, there are still concerns regarding the evolution of antimicrobial resistance, and the risks of toxicity for these surfaces are high.
In addition, biocidal agents that deplete over time also lose their bioactivity [14]. All these limitations highlight the need for new antimicrobial surface coatings. The development of nanotechnology and biomaterials has led to antimicrobial nanoparticles becoming promising candidates in a variety of applications. In addition, with the developments in nanotechnology, the ability of biomaterials coated with antimicrobial nanoparticles to combat microbial adhesion, vitality, and biofilm formation with versatile antimicrobial mechanisms is promising for new-generation implants. However, despite these, there are many difficulties in applying nanoparticles to implant surfaces while preserving their antimicrobial properties [15].

2. Classification of Antimicrobial Nanomaterials

Antibiotic resistance is recognized worldwide as one of the greatest threats to public health. It has been noted that more than 70% of infections caused by bacteria can develop resistance to the main antimicrobial agents used in clinical practice. It has also been determined that approximately 79% of bacteria develop resistance to one or more antibiotics [16]. The effects of antibiotic resistance are not only limited to increased mortality and health complication risks but also lead to increased healthcare costs. The development of new antibiotics is an effective solution to this antibiotic resistance problem. However, the development of new antibiotics often takes years, making it impossible to quickly reduce the immediate problem of antibacterial resistance. In addition, this process is costly, and new antibiotics will only be effective for a limited time until resistance reappears. This has economically hindered the development of new antibiotic classes [17][18]. Therefore, there is a great need to develop a potent antimicrobial agent. Nanoparticles have emerged as new tools that can be used against bacterial infections to help overcome antibiotic resistance and the barriers faced by conventional antimicrobials [19]. Metals, including copper, silver, and zinc, have been used in modern medicine for centuries for infection control due to their antibacterial properties. Nanomaterials containing these metals can be found in various forms, such as nanoparticles of metal or metal oxides and composite materials with different metal layers [20]. With advances in nanotechnology, functional nanomaterials with unique chemical and physical properties have been developed. Nanoparticles with large surface area-to-volume ratio properties offer numerous options for developing agents to treat microbial infections. Metal and metal oxide NPs from this class are very promising candidates as antimicrobial agents [21]. Nanoparticles are materials that show antimicrobial and biocidal activity against bacteria, fungi, and viruses. Nanomaterials derived from gold, silver, titanium dioxide, zinc oxide, and copper oxide are widely used in various fields such as cosmetics, device coatings, and food preservation [22].

2.1. Silver-Based Nanomaterials

Silver-based nanomaterials in different forms such as particles, plates, and wires are used as components in various products and applications [23]. Silver nanoparticles are one of the most studied nanomaterials due to their wide range of applications. These materials are of great interest due to their strong antimicrobial properties against bacteria, viruses, and fungi. In addition, silver nanoparticles (AgNPs) can be applied as disinfectants and exhibit synergistic effects with antibiotics [24].
Silver nanoparticles are used as antibacterial agents in cosmetics, healthcare products, textile fabrics, dressings, and coatings, as well as in clinical applications, e.g., for the treatment of chronic ulcers, antibiotic-resistant diabetic wounds, and burns. In addition, when AgNPs are used in wound therapy, they elicit abundant collagen deposition, which can accelerate wound healing and exhibit anti-inflammatory effects [25]. Silver nanomaterials (especially those with dimensions ≤ 10 nm) are toxic to many human cell lines and cause cytotoxicity depending on factors such as size, time, and dose. To solve this problem, the immobilization of these structures on various support materials such as polymers, activated carbon, metal oxides, and graphene oxide has been investigated. The modification of silver nanoparticles with titanate nanotubes changes their physicochemical properties (such as stability, size, oxidation state, and shape), resulting in enhanced antibacterial, catalytic, and photocatalytic activity [26].

2.2. Gold-Based Nanomaterials

Gold-based nanomaterials can be engineered in various ways to ensure antimicrobial activity. Gold-containing nanomaterials include nanorods, nanolatches, nanoclusters of nanorods, and nanoshells. Optimizing the properties of these substances can be achieved by conjugation with other compounds or by modifying their nanostructure. Antimicrobial activity can also be achieved by the conjugation of gold nanoparticles with antibodies and different antimicrobial agents. Antibiotic-conjugated gold nanoparticles show potent antimicrobial activity against various bacteria and antibiotic-resistant strains [27]. Various metal nanoclusters, such as silver, copper, and gold, are used as antibacterial agents. Gold nanoclusters (AuNCs) from metal nanoclusters have exhibited superior properties in imaging, detection, and biomedical applications. In therapy, AuNCs conjugated with different surface ligands have been widely applied as antimicrobial agents due to their easy modification, polyvalent effects, photothermal stability, and high biocompatibility [28]. Gold nanoparticles have been developed as strong candidates due to their ease of surface functionalization and high biocompatibility [29]. In pharmacology, AuNPs offer anti-angiogenesis, anti-HIV, anti-malarial, antimicrobial, and anti-arthritic activity. Biomedical uses of these materials include gene therapy, drug delivery, diagnostics, and catalysts for medical therapy [30].

2.3. Titanium Dioxide (TiO2) Nanomaterials

The important discovery of ultraviolet (UV) light-mediated water separation on the titanium dioxide (TiO2) surface and various applications of TiO2 nanoparticles, especially nanomedicine and nanobiotechnology, have been widely studied [31]. Titanium dioxide is highly attractive for photocatalytic bactericidal activity compared to other nanoparticles due to its chemical stability, natural abundance, and relatively low cost [32]. In addition, TiO2 nanoparticles are also widely preferred in biological and environmental remediation applications due to their good thermal stability, chemical biocompatibility, unique photocatalytic activity and physicochemical properties, non-toxicity, and high surface-area-to-volume ratio [33]. TiO2 nanoparticles have broad activity against fungi and bacterial microorganisms, and these properties are of great interest for multidrug-resistant strains. In addition, due to the non-contact biocidal effect and environmental friendliness of TiO2-based nanocomposites, it is not necessary to release potentially toxic nanoparticles into the environment to achieve disinfection properties [34].

2.4. Zinc and Zinc Oxide Based-Nanomaterials

The use of inorganic antimicrobial agents against infections offers advantages such as good selectivity, lower toxicity, lower microbial resistance, and higher stability compared to organic antimicrobials. Among them, zinc oxide (ZnO) offers advantages such as high heat resistance, higher selectivity, lower cytotoxicity, and higher stability compared to inorganic antimicrobials. When it comes to antimicrobial application, NPs exhibit superior properties compared to bulk materials. It can improve interactions with cells and optimize antimicrobial activity due to increased contact surface area [35]. Various studies have shown that smaller ZnO NPs have better antimicrobial activity compared to larger nanoparticles [36][37]. The application of ZnO in healthcare products has attracted particular attention because of its UV radiation-blocking capability. It has been supported by various studies that ZnO NPs have antibacterial activity and that these structures have high efficacy against different bacteria [38]. In medicine and biology, the antimicrobial and fungicidal activities of ZnO-NPs, their cytostatic activity against cancer cells, their anti-inflammatory activity, their use in bioimaging due to their chemiluminescent properties, their ability to accelerate wound healing, and their antidiabetic properties are of great interest [39].

2.5. Copper and Copper Oxide-Based Nanomaterials

Copper and copper oxide-based nanomaterials are very interesting due to their unique properties that enable them to be used in many fields such as sensors, optics, solar cells, catalysts, electronics, remediation applications, and antimicrobials [40]. Copper is a highly conductive material and is cheaper than materials such as gold (Au) and silver (Ag). Since CuO phases are more stable thermodynamically than pure copper, most of the synthesized copper nanoparticles (Cu NPs) have surface oxide layers. The CuO nanostructure is also a p-type semiconductor with a monoclinic structure and high dielectric constant [41]. The generally accepted antibacterial action mechanism of copper-based nanomaterials is based on the release of Cu2+ ions. Copper ions can damage the bacterial cell membrane and enter cells to disrupt enzyme function, causing bacterial death [42]. Copper nanoparticles are highly reactive antimicrobial materials due to their high surface-to-volume ratio. Among metal oxide nanoparticles, CuO NPs are of great importance as they are the simplest member of the copper group. CuO NPs are structured with important antimicrobial properties that inhibit the growth of viruses, fungi, bacteria, and algae [43]. Copper-based compounds are materials with highly effective biocidal properties that are often used in pesticide formulations and various applications in the health field [44]. In addition, CuO NPs are widely used for different applications due to their unique properties, optical applications, gas sensors, solar cells, high-temperature superconductors, lubricants, catalytic applications, and medical applications [45].

This entry is adapted from the peer-reviewed paper 10.3390/hygiene3030020

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