Mechanistic study on antibacterial action of zinc oxide nanoparticles synthesized using green route
Graphical abstract
Introduction
Nanotechnology manipulates material at an atomic or molecular level and makes them gain novel properties not exhibited by bulk matter [1]. The field is dedicated to the application of nanosciences and nano-based structure for advanced biotechnology [2]. Uses of physical and chemical means for the synthesis of nanostructures have been greatly replaced by green methods employing the use of various plant parts, bacteria, fungi, and algae. Biosynthesis of the Nano-based structure is particularly very useful for medical applications as they provide us non-toxic, eco-friendly and cheap nanomaterials [3]. Organic sources are employed for biosynthesis of nanomaterials which eliminates the need for using toxic chemicals as reducing agent. Plants are considered as one of the most useful sources for the green synthesis of the nanoparticle as they host a wide range of metabolites which act as both reducing and stabilizing agent. Fig. 1 represents the green synthesis procedure of ZnO nanoparticle and different tools employed for its characterization.
Besides the development of a plethora of drug molecule, bacterial infections are still a major cause of mortality. The origination of multidrug-resistant gene in bacteria is a matter of pressing concern thus, the development of novel drug molecules or vectors which can target bacterial genes more specifically is need of the hour [4]. Development of nanotechnology opens a new horizon for control of multidrug-resistant bacteria and related diseases and infections. Green synthesized nanoparticles surround themselves with a large group of organic phytochemicals which helps in ligand-based complexation with various receptors like proteins, lipid, phospholipid, lipoteichoic acid at the microbial surface. This complexation of nanoparticle with bacteria prevents biofilm formation and their growth [5].
The present study focusses on different antibacterial mechanism or pathways adopted by zinc oxide nanoparticle. It includes a concise literature review highlighting the use of different plant source for the synthesis of differently shaped and sized Zinc oxide nanoparticle. Biomolecules commonly involved in reduction and stabilization of nanoparticles has also been reported in the literature survey. Bacteria used and mechanism assumed or referred is properly formulated in Table 1. Present work also demonstrates the impact of different physiological parameters of nanoparticles like its shape, size, surface charge, concentration on bacterial growth inhibition. The impact of different working conditions like pH and Temperature on the anti-bacterial activity of nanoparticles has also been demonstrated.
Traditional route employs the use of physical and chemical methods for the synthesis of nanoparticles. Physical methods of nanoparticle synthesis like vapor condensation, Interferometric lithography, physical fragmentation and amorphous crystallization require a great deal of space for machine set-up, use of costly equipment and high temperature and pressure conditions for the nanoparticle synthesis process [[6], [7], [8], [9]]. The chemical approach of nanoparticle synthesis includes sol-gel method, solution evaporation method, reduction of precursor molecules like silver nitrate (AgNO3), Gold chloride (HAuCl4), and Zinc acetate dihydrate (C4H6O4Zn · 2H2O) by using non eco-friendly toxic chemicals [10]. Some volume of the chemical may reside in the final nanoparticle product which may interfere with the biological applications and the additional stabilizing agent is also needed to cap the nanoparticle in case of physical and chemical synthesis [[11], [12], [13], [14]]. Thus, use of green chemistry for the synthesis of the nanoparticle is a boon for healthcare industries as it eliminates the need of using toxic chemicals and help in large-scale synthesis of extra pure nanoparticles.
Green synthesis employs the use of plant parts, bacteria, fungus, algae and organic products for the synthesis of nanoparticles [15]. There is no need to add any separate stabilizing agent as plant metabolites itself act as both reducing and stabilizing agent [16]. Phytochemicals may aid to provide specific medical applications to the nanoparticles and they are easy to manipulate at laboratory scale. For instance, nanoparticles synthesized by green route tend to exhibit better anti-bacterial activity than physical or chemical method derived nanoparticles due to the coating of various pharmacologically active biomolecules on their surface which allows multiple ligands based conjugation of nanoparticle with receptors on bacterial membranes. These biomolecules are mainly organic acids, flavones, aldehyde, ketone, amides, polysaccharides, and quinones and known to have significant therapeutic effect against a wide range of human pathogen [17]. Recently, An experiment conducted by K. Gudikandula and S.C Maringanti demonstrated better zone of inhibition obtained through biologically synthesized silver nanoparticle (AgNP) than the chemically synthesized one against bacterial sp. E.coli, S. aureus, B. subtillis and K. pneumonia [18]. Similar results were demonstrated for lemon synthesized silver nanoparticle and tri-sodium synthesized silver nanoparticle as lemon synthesized AgNP depicted better antibacterial activity against both gram-positive and gram-negative bacteria [19].
Shape, size, surface properties and other physiological features can be carefully monitored using characterization tools like UV–Visible spectroscopy (UV–Vis), X-ray diffraction spectroscopy (XRD), Scanning electron microscope (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), elemental dispersive analysis of X-ray (EDAX), Transmission electron microscopy (TEM), Dynamic light scattering (DLS).
Nanoparticles have widely emerged as an anti-bacterial agent in the last decade. The nanoparticle can be used as a personalized medicine because it shows specific targeting and minimum toxicity [20]. They have proven useful for inhibiting antibiotic-resistant bacteria particularly [21,22]. Nanoparticles exhibit their bacteriostatic or bactericidal effect by either blocking their food source or by disrupting their cell membrane. The nanoparticle can accommodate a large number of ligands for better targeting of pathogenic microbes owing to its large surface area to volume ratio. Several types of metal and metal oxide nanoparticles have been already reported to possess anti-microbial property like Silver [23], gold [24], copper [25], Iron [26], Zinc Oxide, titanium oxide [27], copper oxide [28], Iron oxide [29] nanoparticles. ZnO NP has gained considerable attention out of all other nanoparticles because of its unique electronic, optical and medicinal properties [30]. Zinc oxide nanoparticle is highly biocompatible and its electron transport kinetics rate is fast so, it's suitable to use it as a biological membrane or for other biological applications [31]. Review literature clearly illustrates the antimicrobial activity of ZnO NPs against a broad spectrum of pathogenic bacteria like Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella aerogenes, Pseudomonas aeruginosa, Proteus mirabilis, Mycobacterium tuberculosis and Bacillus subtilis. Despite the great anti-bacterial property reflected by nanoparticles, its toxicity is a major drawback. Coating of the nanoparticle can increase its biocompatibility and anti-bacterial property [32].
Section snippets
Review of literature
Synthesis of ZnO NP using different biological route is clearly demonstrated in Table 1. Phytochemicals used for reduction and stabilization of nanoparticle is also mentioned very clearly. These phytochemicals may contribute to the anti-bacterial activity of nanoparticles by starting a cascade of events like ROS generation, enzyme inhibition, disrupting the biofilm formation, protein denaturation, cell membrane integrity disruption or by accelerating the process [65].
Anti-bacterial activity mechanisms adopted by zinc oxide nanoparticles
Nanoparticle adopts a series of mechanism to act as an anti-bacterial agent. Cell membrane integrity loss induced by disruption of phospholipid bilayer is considered as one of the most important mechanism. Oxidative stress induced by Reactive Oxygen Species (ROS) generation is another important mechanism adopted by nanoparticles. This ROS molecule further causes cell death by inhibiting or altering DNA replication, Protein synthesis cycle, food metabolism cycle or Respiratory cycle.
Zinc oxide
Pharmacokinetics of zinc oxide nanoparticles
ZnO nanoparticles get incorporated into the body due to various reasons like inhalation, dermal penetration, ingestion and others [96]. Nanoparticle bioavailability depends upon the route of administration. Gastrointestinal route serves as a first pass barrier and leads to incomplete absorption of ZnO NP while intravenous route of injection directly administers nanoparticles into systemic circulation [97]. The solubility and absorption of nanoparticles depend upon particle size, pH, and
Parameters affecting anti-bacterial activity of ZnO NP
ZnO NP internalization and its mechanistic activity totally depend upon the physicochemical property of NP-like its shape, size, charge, functional groups, surface defects (Fig. 4).
Application of ZnO NPs as an anti-bacterial agent
Use of zinc oxide nanoparticle as an anti-bacterial agent opens new dimension in the field of medicine. Its high anti-bacterial activity enables it to be used for preservation of food items [114], Cosmetics [115], wounds dressing for fast healing [116], for dressing of burns [117], as a disinfecting agent [118], antiseptic ointments or lotions, for coating of medical devices ensuring its safety, water treatment [119]. Zinc Oxide nanoparticle synthesized using Parthenium hysterophorus L. was
Conclusion
The present study presents an extensive report on anti-bacterial activity mechanism adopted by zinc oxide nanoparticle. Nanoparticles can greatly bind to the bacterial surface due to multiple ligands that they possess owing to green synthesis procedure adopted for nanoparticle synthesis. The large surface area to volume ratio allows them to bind to multiple ligand binding sites present on the bacterial cell surface. Different mechanism adopted by gram + and gram – bacteria for nanoparticle
Acknowledgement
The authors gratefully acknowledge DST-SERB (FILE NO. YSS/2014/000931), New Delhi, India to carry out this work.
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