Microbial Interactions at Nanobiotechnology Interfaces. Группа авторов
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1.13 Effects of Functionalization on the Antimicrobial Property of Nanomaterials
Although several antimicrobial agents have been developed so far, they are still not able to meet the required therapeutic index. Even though NMs are well‐known for their renowned antibacterial activities, their application is still limited due to their certain nonspecific toxicity. In order to improve antimicrobial therapeutic index and reduce the nonspecific toxicity, biofunctionalization or chemical modification of NPs with bioactive molecules has emerged as a plausible and promising solution. The selection of a NM along with a rational biomolecule is likely to improve the applicability of the composite NM.
Several techniques have been employed to functionalize NMs such as covalent bonding (Veerapandian et al., 2010), non‐covalent bonding (Knopp, Tang, & Niessner, 2009), simple coating or deposition (Bunker et al., 2007), stober technique (Luckarift et al., 2007), coupling reaction‐assisted immobilization (Wang et al., 2004), reverse micelle and sol–gel technique (Yang et al., 2004). Photo‐Fenton oxidation, radiofrequency plasma, and vacuum‐UV radiation methods have been employed for click chemistry (Mazille et al., 2010). Protein and peptides, especially those with cationic nature, have been found to be toxic against many drug‐resistant microbes. The antimicrobial property of these proteins or peptides depends on the ability to form α‐helical or β‐sheets or α‐helical bundles because of the interaction with anionic bacterial cell wall and self‐association in solution state (Fernandez‐Lopez et al., 2001; Oren et al., 2002). In an earlier study, the antibacterial activity of hen egg lysozyme‐conjugated polystyrene latex NPs against Micrococcus lysodeikticus was studied. It was observed from the study that antimicrobial property of cationic NP‐conjugated enzyme was twice that of free enzyme (Satishkumar & Vertegel, 2008). Similar to proteins, carbohydrate also enhances the antimicrobial property of NMs. Veerapandian et al. (2010) reported that the glucosamine (amino sugar) functionalization of silver NPs improved the antimicrobial property against eight Gram‐positive and Gram‐negative bacteria. The functionalization of glucosamine over silver NPs enhanced the interaction and penetration of NPs into bacterial cell, which improved the antibacterial activity of glucosamine‐functionalized silver NPs (Veerapandian et al., 2010). Next to proteins and carbohydrates, lipids also possess antimicrobial property and they are part of innate immune system. The common antimicrobial lipids found in skin cells of human involve sphingosine, dihydro‐sphingosine, 6‐hydrosphingosine, sapienic– acid, and lauric acid (Drake et al., 2008). A study reported that oleic acid‐stabilized silver NPs exhibited highest antimicrobial property against E. coli and S. aureus. It was observed that the hybrid material produced a quick response over E. coli than S. aureus. The stabilization of oleic acid improved the permeability of the NP inside the bacterial cell, which inhibited or altered the cellular transport across the bacterial cell and resulted in bacterial cell death (Le et al., 2010). Apart from other biomolecules like proteins/peptides, carbohydrates, lipids, and DNA, the NMs have been functionalized with antibiotics to improve their antibacterial effect through synergistic effect. It was reported earlier that the introduction of antibiotics such as kanamycin, erythromycin, ampicillin, and chloramphenicol along with silver NPs has enhanced the antibacterial property of silver NPs (Fayaz et al., 2010). The ampicillin silver NP complex has shown the highest antimicrobial effect over other complexes. Here, the strong van der Waals attraction force caused the interaction of NP with the bacterial cell surface. This interaction led to the lysis of cell wall and subsequent penetration of NP into cell where it intervened with the DNA unwinding and effected in the death of bacterial cell (Fayaz et al., 2010). In another study, Jaiswal and Mishra (2018) showed that the functionalization of silver NPs with curcumin improved the antimicrobial properties and also reduced the cytotoxicity of the silver NPs against human keratinocytes (Jaiswal & Mishra, 2018). However, in recent years a lot of work is going on with functionalization of NMs and the basic understanding of the interaction of the bacterial system with functionalized NPs. Better understanding of mechanism of functionalized NMs along with suitable nano‐bio interface phenomenon will guide us to develop more standard design criteria to develop advanced materials with peculiar and desired properties.
1.14 Conclusion and Future Perspectives
This section delineates an overview of NMs, their role in microbial resistance, and the effect of physicochemical factors on their antimicrobial property. The development of microbial resistance to antibiotics and other common disinfectants has driven researchers to look for novel strategies to treat infections. Pertaining to this issue, NMs have emerged as a promising solution to microbial resistance due to their broad spectrum of antimicrobial property along with ease of integration with other products for diverse applications. It is clear from the literature that the antimicrobial property of the material depends on certain crucial physicochemical properties such as size, shape, and surface chemistry. Further, the antimicrobial property of the system can be tuned by controlling those crucial physicochemical properties of nanostructures. Understanding of this phenomenon can be exploited to tailor NMs of interest with reduced nonspecific toxicity where the NMs can be engineered to be specifically active against microbial cells rather than mammalian cell systems. The discussion over the mechanism of action of metal and metal oxide NMs suggested that the mechanisms of action of these NMs are not merely dependent on the release of metal ions from the NMs but also depend on the nanostructures (size and shape) of the NMs, which contribute directly to the antimicrobial property of the NMs. In the present scenario, the toxic effect of NM systems and the mechanism of action over human systems are not clearly understood. All these issues can be addressed if we develop standardized testing protocols and define the NMs' properties on an international level and enforce it. Most importantly, future research in this field should be directed to further understand the complex relationship between the various physicochemical factors over the antimicrobial property and mechanism of action of the NMs.
Questions and Answers
1 Why the study of the nano‐bio interface is necessary?Bio–nano interface hosts “the dynamic physicochemical interactions, kinetics and thermodynamic exchanges between nanomaterial surfaces and the surfaces of biological components.” In the last three decades, there has been an exponential increase in the application of nanomaterials in various fields including the health sector. This is leading toward a long‐term co‐existence of such nanomaterials with living systems which may result in adverse toxicological effects to the living bodies. In this regard, it is necessary to study the effect of these materials on the biological entities such proteins, DNA, RNA, cell membrane, cell organelles, cells, tissues, and organs.
2 Do nanomaterials occur in nature?Yes, nanomaterials do occur in nature and are called “natural nanomaterials.” They are produced by biological species or anthropogenic activities in nature without human intervention. The nanomaterials formed in nature are present throughout the earth's atmosphere, hydrosphere, and lithosphere, such as in volcanic ash, sea spray, and smoke.
3 Explain the terms “antibiotic resistance” and “post‐antibiotic era”?“Antibiotic resistance” is the ability of microbes such as bacteria to resist the killing effects or overcoming the actions of the antibiotics. In recent times, a rapid increase in the level of microbial resistance to antibiotics is leading to an era called as “Post‐antibiotic era” where the mortality rate caused because of microbial infections will be higher than that of cancer as stated by Centre for Disease Control and Prevention.
4 How