Review On Antibacterial Mechanisms of Nanoparticles and The Latest Developments in Antibacterial Applications

Divya Mehta, Himanshu , Aarti Kumari, Kushi Deora, Rishabh ,

doi:10.5281/zenodo.15834715

Review Paper | Open Access
Volume 03 | Issue 07 | Article Id IJPS/250307097

Review On Antibacterial Mechanisms of Nanoparticles and The Latest Developments in Antibacterial Applications
Divya Mehta* Himanshu Aarti Kumari Kushi Deora Rishabh
Department of Chemistry, BM College of Pharmacy, Farrukh Nagar, Gurugram, Haryana.

Abstract

Nanoparticles (NPs) have drawn a lot of interest as novel antibacterial agents because of their distinct chemical and physical characteristics. Since NPs have several antibacterial activity modes, they are less likely to cause resistance development than traditional antibiotics. Reactive oxygen species (ROS) production, bacterial cell membrane disruption, disruption of intracellular components such proteins and DNA, and the development of oxidative stress that results in cell death are important pathways. This review explores the antibacterial mechanisms of various nanoparticles such as Silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO?), and copper (Cu) nanoparticles with unique antibacterial qualities. Recent developments in nanotechnology have made it possible to create hybrid and multipurpose nanoparticles with improved antibacterial activity and targeted delivery. For regulated medication release, smart nanoparticles that react to environmental cues like PH or temperature are being investigated. In order to stop bacterial contamination and illness, NPs are also being included into food packaging, water purification systems, medical device coatings, and wound dressings. Despite their potential, questions still surround the long-term safety, environmental effects, and cytotoxicity of nanoparticles. Optimizing NP production, enhancing biocompatibility, and comprehending their interactions with biological systems are the main areas of ongoing research. All things considered, nanoparticles offer a viable platform for next-generation antibacterial tactics, especially when it comes to combating antibiotic resistance and enhancing public health outcomes.

Keywords

Nanoparticles, Antibacterial mechanisms, Reactive oxygen species (ROS), Cell membrane disruption, Latest developments

Introduction

Nanotechnology has slowly yet severely taken over different industries worldwide. This rapid place of technological revolution can especially be seen in the developed world, where nano scale markets have taken over rapidly in the past decade. Nanotechnology is not a new concept since it has now become a general-purpose technology shown in (figure 1). Nanotechnology is considered as a prevailing tool and technique in medical technology as well as almost every filed life ^[1]. Nanotechnology applications are highly suitable for biological molecules, because of their exclusive properties. The field of nanotechnology is one of the upcoming areas of research in the modern field of material science and biological science ^[2]. Nanotechnology is going to revolutionize the world. For pharmacists, the applications of nanotechnology mean drugs containing nano-sized active ingredients. The smaller drug delivery systems allow deposition of medications in previous inaccessible areas of the body; it also has a great importance in the treatment and diagnosis of certain diseases as cancer ^[3].A recent discovery in the drug delivery form is target therapy and improving the diagnostic tests and medical devices. But with the advances comes concern, the science behind nanotechnology is still in its’ original state ^[4]. According to the National Nanotechnology Initiative (NNI), nanotechnology refers to the study of all particles have about 100 nanometers or less. A nanometer is one-billionth of a meter in size ^[5]. One of the most important advantages of the smaller particle size is the ratio of surface atom or molecules to the total number increases. That means they have large surface areas which lead to increase their surface activity and produce changes in their physical properties, and biological properties ^[6].

Figure.1: Nanotechnology has gained significant momentum in recent decades, becoming a major area of scientific and technological development

Nano science is the study of unique properties of material between 1-100 nm and nanotechnology is the application of such research to create or modify novel objects. Commonly known as nanoscale surface area and quantum mechanical effect become important in describing properties. In recent years, a variety of materials have been synthesized into nanoparticles using the synthesis of nanoparticles from solution techniques. These materials tiny size gives them unique qualities and creates the potential for creative uses ^[7]. There was interest in the new disciplines of nanotechnology and nanoscience at the start of the twenty- first century. The twentieth century has been completely transformed by developments in nanotechnology and its applicability to the pharmaceutical and medical industries ^[8]. The simplicity and affordability of the aqueous colloidal synthetic approach make it a desirable avenue for aqueous synthesis. To produce structures and gadgets at the nanoscale, wet nanotechnology uses biological systems in aquatic conditions shown in (figure 2). It focuses on working with molecules and assembling them into larger structures from smaller parts; this frequently involves enzymes, membrane, and genetic material ^[9]. Dry nanotechnology manipulates and fabricates nanomaterials and structures by applying the principles of physical chemistry in a dry, liquid-free environment. Solutions for spray drying polymeric and non-polymeric nanoparticles shown in (figure 2). At the evaporating front of the droplets, the solutes and nanoparticles gather and create a shell that dries to become the hollow microparticle ^[10].

Figure 2: Wet, dry, and computational nanotechnology represent distinct approaches to manipulating materials at the nanoscale

The computational nanotechnology is to investigate, evaluate, and forecast the behavior of material and systems at the nanoscale using computer-based models, to store, control, analyze and envision nanobiotechnological knowledge, computational chemistry and traditional bioinformatics methods are needed Shown in (figure 2). Thus, a new field known as nano informatics combines the most modern and most advanced bioinformatic and computational chemistry methods ^[11].

Nanoparticles

The term "nanoparticle" typically refers to inorganic materials rather than individual molecules. This is the reason why nanoparticles and ultrafine particles are used interchangeably: in the 1970s and 1980s, when Granqvist and Buhrman of the United States were doing the first comprehensive fundamental investigations with nanoparticles, which were referred to as ultrafine particles in Japan. In essence, nanoparticles serve as a link between atomic or molecular structures and bulk materials, which makes them of scientific interest. The nanoscale, size-dependent properties are observable, whereas the physical properties of a bulk material remain constant regardless of its size ^[12]. The most basic building block of a nanostructure is a nanoparticle, which is larger than an atom or a simple molecule, which are subject to quantum mechanics, but much smaller than the world of common things, which are described by Newton's laws of motion. One of the primary features and attractions of a nanoparticle is its optical property. For instance, a 20-nm gold nanoparticle has a distinctive wine-red color. A nanoparticle of silver is grayish yellow. Nanoparticles of palladium and platinum are black ^[13]. Any tiny particle with a diameter between 10 and 1000 nm is called a nanoparticle. Researchers have focused a lot of emphasis on the nanoparticles' unique physical, chemical, and biological characteristics. Particularly intriguing are nanoparticles because of their extraordinary and phenomenal characteristics. These nanoparticles fall into a number of different groups, including copper, zinc, silver, and gold. Over 1814 goods that are enabled by nanoparticles have been produced employing NPs ^[14]. The extremely high surface to volume ratio of nanoparticles ratio upon them certain characteristics that distinguish them from the identical material in bulk and are advantageous in various areas include photonics, electronics, biomedicine, catalysis, etc. Water treatment, solar energy conversion, biomedicine, and catalysis all make use of this characteristic of nanoparticles. NPs is the most popular novel material employ as a nanoparticle because to its antibacterial catalytic qualities and lack of toxicity to humans ^[15].

Types Of Nanoparticles

Organic nanoparticles: Organic NPs are solid particles composed of organic compounds like lipids or polymers shown in (figure 3).

Liposomes: - The most well-known and adaptable assemblies in drug delivery systems are phospholipid vesicles, or liposomes. When a self-forming encapsulated phospholipid bilayer comes into touch with an aqueous solution, liposomes are discovered. Liposomes are uni or multilamellar vesicles made of phospholipids that can be synthesized or naturally occurring. They are easily large-scale, biodegradable, and non-toxic ^[16]. Food technologists have exciting opportunities with nanoliposome technology in areas like food ingredient encapsulation and controlled release, as well asenhanced bioavailability and stability of delicate materials ^[17].

Figure 3: Nanoparticles are generally classified into organic, inorganic, and carbon-based types

Polymeric: - Polymeric nanoparticles One of the most often used materials is polymeric nanoparticles because of their ease of synthesis and ability to be processed into a variety of features needed to create effective drug delivery systems. The use of polymeric nanoparticles has expanded over the past few decades, drawing the attention of numerous research teams. It is essential for many different types of drug delivery systems to overcome a number of their drawbacks and offers a compelling substitute for the long-term delivery of therapeutic agents for chronic administration ^[18].

Micelles: - A hydrophilic polar surface and a hydrophobic fatty acid core characterize micelles, which are closed lipid monolayers. When lipids in solution reach a concentration higher than the lipid's critical micelle concentration, they assemble into micelles. The relative proportions of the hydrophobic tails and hydrophilic headgroups of lipids that form liposomes and micelle-forming lipids distinguish the two types of lipids. If the headgroup is significantly larger than the tail, the molecule will form a micelle and resemble a cone ^[19].

Dendrimers: - The early 1980s saw the emergence of dendrimers as stunning, star-shaped, branching molecules with minimal polydispersity and flawless structure from the sea of polymer sciences. However, as early as 1941, Flory had the initial notion for creating branching molecules. Analytical and synthetic techniques were not yet developed enough to experimentally support such a notion, as was the case with numerous discoveries that were ahead of their time ^[20].

Inorganic nanoparticles: Inorganic nanomaterials composed of non-carbon-based elements and compounds shown in (figure 3).

Silver nanoparticles: - Silver NPs are metallic nanoparticles known for their potent antibacterial activity against various bacteria. The development of inorganic nanomedicine is also being thoroughly investigated in the therapeutic area of antibacterial therapy. Many metal ions have the potential to be antibacterial agents, particularly silver ^[21].
Zinc oxide nanoparticles (ZnO-NPs): - zinc oxide NPs are one of the metal oxide nanomaterials and a versatile inorganic compound. Exhibit excellent antibacterial properties and biocompatibility, making them suitable for biomedical applications. The antibacterial qualities of zinc oxide nanoparticles (ZnO NPs) make them one of the most popular nanoparticulate materials. Ampicillin 250, ampistar 250 and gercillin 250 medicines created with the help of ZnO Nps as antibacterial ^[22].
Copper oxide nanoparticles (CuO-NPs):- CuO nanomaterials show significant antibacterial activity against gram-positive and gram-negative bacteria. CuO nanoparticles exhibited greater affinity for the bacterial cells and more effective antibacterial action. CuO NPs' antibacterial efficacy against Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus casei, and three oral Candida species—C. albicans, C. krusei, and C. glabrata—was examined ^[23].
Iron oxide nanoparticles (FeO-NPs):- Iron oxide NPs are tiny particles of FeO with superparamagnetic properties and bind to sulfhydryl compounds in bacterial cells, exerting antibacterial effects. The capacity of iron oxide nanoparticles (IONPs) to rupture bacterial cell membranes, produce reactive oxygen species (ROS), and possibly denature bacterial enzymes makes them interesting antibacterial agents ^[24].

Carbon-based nanoparticles: Carbon-based NPs composed of carbon atoms shown in (figure 3).

Carbon black nanotubes: - Carbon black nanotubes Heavy petroleum feedstock can be partially burned to produce carbon black (CB), a substance made up of finely split particles. Complex separation and purification methods, advanced equipment, and chemical pre-treatment are all necessary for the commercial production of CB nanoparticles. Rubber that has been cleaned can also create CB nanoparticles, although the procedure is technically challenging ^[25].
Quantum dots: - Quantum dots (QDs) and/or semiconductors are nanocrystals made of semiconductor materials that have quantum mechanical properties. These materials include zinc sulfide (ZnS), cadmium sulfide (CdS), cadmium selenide (CdSe), and cadmium telluride (CdTe). The applications of QDs is biological imaging and labeling, lasers, light-emitting diodes (LEDs), and solar cells. To alter their surface characteristics for specific applications and stop aggregation, QDs are typically stabilized or coated ^[26].

Synthesis of Nanoparticles

There are two primary methods for creating nanoparticles. Traditionally, the process of creating fine particles has been "top-down," which refers to attrition reduction and other conventional comminution techniques. Production methods that use "bottom up" strategies shown in (figure 4) have become more and more popular in recent years. When a material is built up from the bottom-up atom by atom, molecule by molecule, or cluster by cluster it is referred to as a bottom-up approach. Both strategies are crucial to contemporary industry and perhaps to nanotechnology as well ^[27]. The "top-down" method involves using an outside force to break down solid materials into smaller pieces. According to this method, numerous physical, chemical. In order to supply the energy required for the creation of nanoparticles, thermal procedures are employed.
The second strategy referred described as "bottom-up," collects and combines atoms or molecules of gas or liquid. Compared to one another, these two strategies offer benefits and drawbacks ^[28].

Figure 3 Nanoparticles can be synthesized using a variety of methods, broadly categorized as top down and bottom-up.

Nanoparticles have been created using a variety of methods. These include biological (plants, fungi, bacteria, viruses, yeast, etc.), chemical (sol-gel, solvothermal, co-precipitation, pyrolysis, chemical redox reaction, etc.), and physical (laser ablation, arc discharge, photolithography, ball milling, etc.) techniques. The use of hazardous chemicals and solvents in physical and chemical processes can have a negative effect on the environment. Biological synthesis of NPs employs natural resources and more biocompatible, it has drawn a lot of attention as an alternative. Over the past five years, plant-based NP synthesis has attracted a lot of attention ^[29].

Antibacterial

One of the biggest causes of morbidity and mortality in the world today is still bacterial infections. Bacterial resistance to antimicrobial agents is a significant worldwide public health issue, per the World Health Organization's report. Increased bacterial resistance is mostly linked to the lack of novel, potent antibacterial drugs. In order to address the issue of antimicrobial resistance, this has spurred efforts globally to create more potent antibacterial chemicals. Researchers are exploring every avenue to address the issue of antibiotic resistance since the scientific community is extremely worried ^[30]. Antibiotics are frequently used as the first line of treatment for various infections. According to Ewald (1980), antibiotics dramatically suppress the growth of many microorganisms and lessen the symptoms that go along with them. However, the anticipated advancement of the treatment option has been hampered by the development of microbial resistance to these antibiotics, medication addiction, and antibiotic discharge into the environment A significant and promising approach is the use of nanoparticles to treat bacterial infections. New nano-antimicrobials utilizing quorum sensing nano-inhibitors are anticipated as a result of advancements in nanotechnology, particularly the creation of methods and technologies for creating NPs with unique properties ^[31]. A popular and powerful tool in the battle against infectious diseases are antibiotics. However, antimicrobial resistance one of the major risks to public health has been brought on by the careless, excessive, and improper use of antibiotics. According to estimates, antimicrobial resistance will surpass cancer as the leading cause of death by 2050, potentially accounting for almost 10 million deaths annually. This circumstance has compelled the hunt for novel defenses against bacterial illnesses. There haven't been enough new antibiotic discoveries in the past 25 years because of their high cost and other exploration and design challenges. The ability to build NPs with desired qualities has begun to emerge as a viable technique thanks to advancements in nanotechnology. Metal nanoparticles (NPs) have garnered significant attention as antibacterial agents due to their distinct characteristics. The antibacterial properties of several metal nanoparticles (NPs), such as iron oxide (Fe3O4), zinc oxide (ZnO), copper (Cu), selenium (Se), nickel (Ni), gold (Au), and silver (Ag), have been thoroughly investigated ^[32]. Nanotechnology alters a substance's physico-chemical characteristics, opening new biological application possibilities. Recently, it has been found that many NPs are effective against a variety of diseases, including germs that are resistant to antibiotics. NPs' antibacterial properties are influenced by a number of critical criteria, including their size, surface area, shape, net charge, and physicochemical characteristics. The ratio of surface to volume rises dramatically as the NPs' size falls. Greater interaction with bacteria and a significant impact on their antimicrobial actions are provided by NPs with large surface areas. It has been observed that positively charged metal nanoparticles (NPs) exhibit more antibacterial activity and form a stronger bond with negatively charged bacterial surfaces ^[33].

Prevention of Antibiotic Resistance

Nanoparticles can help prevent antibiotic resistance while providing creative solutions to the problems posed by bacterial resistance development through a variety of processes. Nanoparticles can help mitigate antibiotic resistance ^[34]. Nanoparticles can be engineered to transport therapeutic payloads with several modes of action or numerous antimicrobial agents. By simultaneously addressing several targets in bacteria, this method makes it more difficult for them to become resistant to all methods. Synergistic effects can arise when conventional antibiotics and nanoparticles are combined. Antibiotic concentrations may be lowered by the nanoparticles, increasing antibiotic efficacy and lowering the selective pressure for the emergence of resistance ^[35]. Bacteria use efflux pumps to pump out antibiotics, they frequently acquire resistance. It is possible to design nanoparticles to block these efflux pumps, which would stop drugs from leaving bacterial cells and increase their potency. The biofilms of bacteria are resistant to drugs. Since nanoparticles are small and have certain qualities, they can more easily pass through biofilms, reach bacteria that are embedded in the matrix, and circumvent one of the processes that lead to antibiotic resistance ^[36].

The prevention of cross-resistance, in which resistance to one antibiotic confers resistance to another with similar mechanisms of action, may be aided by nanoparticles having different mechanisms of action. Creating nanoparticles with a variety of antibacterial techniques will help achieve this. Antimicrobial drugs can be delivered specifically to the infection site through the use of nanoparticles in targeted medication delivery. This lowers the total selective pressure for resistance by limiting the amount of antibiotic exposure that bacteria in other areas of the body receive ^[37].

Antibiotic dosages can be decreased by using nanoparticles to increase the therapeutic effectiveness of antibiotics. By lessening the strength of the selective pressure on bacteria, lower doses may lessen the chance that resistance may develop. When many antimicrobial treatments, such as antibiotics and non-traditional antimicrobial agents, are employed concurrently, combination therapy can be facilitated by nanoparticles. By targeting bacteria via distinct processes, this strategy makes it more difficult for them to become resistant ^[38].

Figure 5: Nanoparticles exert their effect through various mechanism, including anti-microbial activity, drug delivery, and cell signaling

The exact mechanism underlying NPs' antibacterial qualities is currently unknown. The particles' ability to (i) attach to the bacterial cell, hinder respiration and cell membrane permeability, (ii) release free metal ions from the NPs' surface, or (iii) induce oxidative stress by producing reactive oxygen species (ROS) shown in (figure 5) are some of the main mechanisms that result in cell death. The most suggested methods are listed in Figure 5. The mechanisms differ based on the type of NP. Ag and Au are believed to have bactericidal effects primarily through the release of metal ions, while metal oxide nanoparticles (NPs), such as ZnO and TiO2, are assumed to have bactericidal effects primarily through the formation of ROS ^[39]. AgNPs have been found to have a deadly effect because they directly interact with the bacterial cell wall before penetrating into the cytoplasm. The bacterial cell wall and membrane get coated with NPs, which results in morphological alterations such cytoplasm shrinkage, membrane separation, the development of many electron-dense pits, and ultimately membrane breakage. It has been demonstrated that the pits formed by NP deposition in the E. coli cell wall release lipopolysaccharide molecules and membrane proteins, causing the outer membrane to become less intact and ultimately leading to cell death ^[40]. Metallic ions can be produced by chemically oxidizing metals in aqueous solutions. NPs can release more ions under aerobic circumstances than bulk materials because of their larger surface-to-volume ratio. The antibacterial activity of NPs is significantly influenced by the released ions from their surface. Because of their nanoscale size, NPs can readily penetrate and pass through bacterial cell walls and interact with the cell membrane after initially attaching to them. They break down the integrity of the cell membrane and increase its permeability by releasing ions that alter its structure. Consequently, they lead to cell death and the release of cell contents. In addition to lowering intracellular ATP levels and blocking oxidative phosphorylation, NPs that target the cell membrane also affect membrane potential and proton motive force. Such an antibacterial effect of spherical AgNPs against E. coli was revealed by proteomic studies, which showed that exposure to AgNPs has led to the build-up of envelope protein precursors implying disruption of proton motive force ^[41]. The carbonyl, amino, phosphate, and sulfhydryl (thiol) groups of biological macromolecules, including DNA, proteins, and lipids, are also impacted by free metal ions once they enter the cell. It has been demonstrated that free Ag ions preferentially bind with bacterial nucleic acids through nucleosides as opposed to phosphate groups, breaking down chromosomal DNA or preventing DNA replication. Metal ions, like Ag+, also interact with proteins' and enzymes' thiol groups, changing their three-dimensional structure and obstructing their substrates' active binding sites. When proteins on the membrane and cell wall are interfered with, the bacterial cell wall is broken, the electron transport chain is hampered, and the respiratory process and cell development are inhibited. They interfere with the cytoplasmic proteins needed to produce ATP, rendering them inactive and affecting the way cells function. Additionally, by denaturing ribosomal components and preventing the ribosome subunit from attaching to tRNA, ions inhibit the production of proteins. AuNPs exhibit antibacterial activity against E. coli via collapsing membrane potential and lowering ATP levels by blocking ATPase function and preventing the ribosomal subunit from binding to tRNA, as demonstrated by transcriptomic and proteomic techniques ^[42]. The antibacterial activity of NPs also targets signal transduction in bacteria. Their signal transduction process allows bacterial colonies to thrive in a wide range of environments by being sensitive to and responding to a number of environmental stimuli. This pathway is frequently targeted in the development of antimicrobial drugs since it is known to be essential for the survival and proliferation of bacteria as well as the expression of virulence factors. A physical or chemical signal is sent across a cell in this cell signaling system as a series of molecular pathways, usually protein phosphorylation mediated by protein kinases, which ultimately leads to a cellular response. By changing the phosphorylation pattern of the tyrosine residues of the important proteins, AgNPs 10–15 nm in size were proposed to disrupt the signal transduction and cause bacterial death or growth suppression [^43]. The release of ROS within the bacterial cell is another essential mechanism of the NPs' antibacterial action. ROS are essential for various cellular signaling pathways and are produced during normal oxygen consumption. During oxidative phosphorylation, oxygen serves as the last acceptor of electrons carried by ETS before being reduced to the water molecule. Molecular oxygen absorbs some of these electrons, forming O2-, which can subsequently be converted to H2O2 and •OH. However, metal ions released from NPs' surfaces cause ROS bursts by interfering with respiratory systems and can significantly enhance intracellular ROS generation when bacterial cells are exposed to NPs. By disrupting membrane integrity, deactivating cellular enzymes, upsetting the electron transport system, and lowering membrane potentials, released metal ions further exacerbate the formation of intracellular ROS. To combat oxidative stress, bacteria have built-in antioxidant defense mechanisms. Their inherent antioxidants, like as ascorbic acid and carotenes, guard against lipid peroxidation and other stressors brought on by ROS. They also possess enzymes that change hazardous reactive oxygen forms into less toxic or non-toxic forms, including catalase, peroxidase, and superoxide dismutase. NP exposure, however, causes ROS to build up to an excessive amount, making it impossible for bacteria to withstand harmful alterations in essential cellular components such the cell wall, cell membrane, DNA, and protein. This leads to the accumulation of chemically highly reactive ROS and ROS-induced oxidative stress in the bacterial cell, which damages chromosomal DNA and proteins, causes lipid peroxidation and hole development in the cell membrane, and finally results in cell death. Through oxidative stress, ZnO NPs and TiO2 exhibit their antibacterial properties. They use their strong oxidizing ability to create free radicals, which kills bacteria. They can cause oxidative stress and DNA damage, which lowers E. coli's viability [44]. Gram-positive and Gram-negative bacterial species are affected differently by NPs because of the variations in their cell wall architectures. According to numerous research, NPs have more potent antibacterial effects on strains of Gram-negative bacteria than on strains of Gram-positive bacteria. Gram-negative bacteria have a thin peptidoglycan layer and extra lipopolysaccharides (LPS), whereas Gram-positive bacteria have a thick peptidoglycan layer made up of numerous additional layers. discovered that Gram-negative bacteria were far more affected by NPs than were Gram-positive species. Additionally, other studies indicate the contrary. Investigated the antibacterial activity of ZnO-NPs against Gram-negative E. coli and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus and reported that the antimicrobial effect was stronger in Gram-positive bacterium ^[45].

Synergistic Effect of Nanoparticles with Antibiotics

Antibiotic resistance can be overcome and their efficacy increased by combining NPs with antimicrobial drugs. Furthermore, they can lessen the toxicity and dosage of antibiotics that must be taken. Because NPs affect bacteria through a variety of sites and/or pathways, it is extremely difficult for the microbe to develop resistance. In other words, there is very little chance that the simultaneous mutations required for resistance development will occur. Furthermore, when NPs and antimicrobials are combined, this is even less likely to occur. Consequently, the combination of NPs and antibiotics is seen as a strategy to stop the development of bacterial resistance ^[46]. Nanoparticles and antibiotics work better together to combat drug-resistant bacteria as well as Gram-positive and Gram-negative bacteria. AgNPs in combination with bacitracin, ciprofloxacin, tetracycline, and cefixime had synergistic efficacy against P. aeruginosa, E. coli, S. aureus, and Candida albicans, according to Aabed and Mohammed. showed that the presence of AgNPs significantly enhanced the synergistic action of antibiotics (azithromycin, cefotaxime, cefuroxime, fosfomycin, and chloramphenicol) against E. coli when compared to the antibiotic used alone. CuO NPs and cephalexin together had a synergistic impact against E. coli in another investigation ^[47].

Nanoparticles As Antimicrobial Agent in NP-Drug Conjugate System

NPs are more effective against resistant microorganisms when combined with other antimicrobial agents and customized ^[48]. Because of their chemical characteristics, nanoparticles can bind to antibiotic targets for an extended period of time and provide protection from enzymes ^[49]. Higher antibiotic requirements are thus avoided. To avoid multidrug-resistant pathogenic microbial infections, it is crucial to develop conjugates of antibiotic nanoparticles ^[50].NPs and antibiotics work better together to combat drug-resistant bacteria as well as Gram-positive and Gram-negative bacteria. AgNPs in combination with bacitracin, ciprofloxacin, tetracycline, and cefixime had synergistic efficacy against P. aeruginosa, E. coli, S. aureus, and Candida albicans, according to Aabed and Mohammed. showed that the presence of AgNPs significantly enhanced the synergistic action of antibiotics (azithromycin, cefotaxime, cefuroxime, fosfomycin, and chloramphenicol) against E. coli when compared to the antibiotic used alone. CuO NPs and cephalexin together had a synergistic impact against E. coli in another investigation. The physical (hydrophobic, host-guest, and electrostatic) and chemical (with amine, trans-cyclooctene, hydrazide, isothiocyanate, sulfhydryl, and azide groups of medication) interactions provide the foundation for the production of conjugated NPs ^[51]. Related possible pathways of some antibacterial nanoparticle-drug conjugate formations are presented below.

The NPs improve the permeability and allow more antibiotics to enter the bacterial cell by attaching to the proteins in the bacterial cell membrane. NPs' active surface damages membranes, interferes with protein-protein interactions, and impairs cellular metabolism.
By forming R-S-S-R bonds with sulfhydryl (-SH) groups in the cell wall, NPs prevent respiration, which leads to cell death. When NPs get within bacteria, they may have an impact on respiration and permeability of the cell membrane.
Hydrogenating NPs makes them more stable and hinders their capacity to function by attaching to the bacterial cell's negatively charged surface.
The More antibiotics are able to enter the bacterial cell as a result of the NPs' increased permeability caused by their binding to the proteins in the cell membrane. NPs' active surface damages membranes, interferes with protein-protein int eractions, and causes metabolic problems in cells.
They also interact with the cell wall's sulfhydryl (-SH) groups to form R-S-S-R bonds and prevent respiration, which kills cells. When NPs get inside bacteria, they can alter the permeability and respiration of the cell membrane.

Combining antibiotics with NPs is unlikely to result in the development of antimicrobial resistance since the same microbe must undergo numerous simultaneous mutations. Numerous conjugates remain undiscovered ^[52]. Therefore, new antimicrobials are waiting to be discovered.

Pharmacology And Toxicity of Nanoparticles

Physicochemical characteristics (morphology, composition, size, charge, etc.), exposure route (topical, intramuscular, intradermal, parenteral, and subcutaneous), dosage, and animal species are some of the variables that affect NP pharmacokinetics ^[53]. Oral, cutaneous, or pulmonary routes typically result in limited absorption of AuNP, AgNP, or TiO2 NPs. Depending on size, oral absorption of AuNPs is approximately 0.01–5%, that of AgNPs is 1–4.2%, and that of TiO2 NPs is 0.01–0.05%. Inhalational absorption of AuNPs varies from 0.06% to 5.5% ^[54]. For therapeutic benefits, it is usually preferable for NPs to accumulate excessively in the target tissue; on the other hand, high levels of distribution or accumulation to non-target tissues may cause unintended harm ^[55].To better understand the mechanism and dose variations in the pharmacokinetics of NPs, more investigation is required. Despite their benefits, nanoparticles have the potential to harm biological organisms. Nanoparticles' exceptional physicochemical qualities have led to their application in a wide range of industrial sectors, including food, cosmetics, medicine, textiles, and automobiles ^[56]. Humans are continuously exposed to nanoparticles by inhalation, ingestion, skin contact, and intravenous injection routes, concomitant with their growing use in daily life. Long-term exposure to NPs may be dangerous. It is currently unclear how NPs interact with bodily tissues and, consequently, how harmful they are. Depending on the type of cell line, exposure route, dose and time, and NPs' physicochemical characteristics, different effects are expected ^[57].Ag NPs' toxicity has been thoroughly investigated in vitro, and it has been shown that they are more detrimental to cell lines than other metal NPs ^[58]. It has been noted that negative health impacts rise in tandem with the magnitude of the NP ^[59]. When administered intravenously, NPs can accumulate in the lymphatic system, colon, liver, and spleen ^[60]. NP inhalation may result in lung cytotoxicity ^[61]. NPs are small enough to penetrate the bloodstream and go to the lungs, liver, kidneys, and reproductive organs once they are within the body. Here, they can build up and interact with tissues, causing organ malfunction and cytotoxicity ^[62]. Furthermore, NPs can even cause neurotoxicity because of their extremely small size and ability to pass across the blood-brain barrier. The potential for the usage of NPs' antibacterial qualities to kill off beneficial human microflora is another worry ^[63]. NPs are known to be cytotoxic, carcinogenic, genotoxic, apoptosis inducer, and cell proliferation inhibitor ^[64]. Negative effects caused by NPs in living things usually occur by the destruction of cell membranes ^[65].and organelles or by binding to biomacromolecules and changing their structures and functions ^[66]. Several in vivo investigations have indicated that NPs are harmful. Albino Wistar rats were repeatedly exposed orally to magnesium oxide (MgO) nanoparticles (NPs) for 28 days. This elevated the concentration of hepatic enzymes in the blood and damaged DNA, chromosomes, proteins, and enzymes ^[67]. A study conducted on rats revealed that CuO NP-induced oxidative stress interacts with cell components to generate hepatotoxicity and nephrotoxicity ^[68]. Through glial cell activation, Ag-NPs and TiO2-NPs impact the central nervous system and induce neuroinflammation by releasing proinflammatory cytokines and producing nitric oxide and reactive oxygen species ^[69].AgNPs have been examined for their cytotoxic effects on DNA, the circulatory and respiratory systems, osteoclasts and osteoblasts, and anomalies in embryonic development ^[70]. In addition, NPs have the ability to harm blood coagulation systems and induce hemolysis. NPs' utility in clinical applications is limited due to their slight-known adverse effects; further research is required to maximize the benefits of NPs. The regular application of NPs in the fight against diseases brought on by bacteria that are resistant to several drugs will be made possible by elucidating their toxicity through thorough in vivo and clinical research ^[71].The use of antioxidants is one strategy to lessen the detrimental effects of NPs on living things. It has been observed that utilizing antioxidant compounds has positive effects, particularly in toxicities related to oxidative stress production caused by NP. Safe NP administration also depends on adjusting the exposure duration and threshold dose to prevent cell viability ^[72].

Latest Developments of Nanoparticles in Antibacterial Application

Smart nanoparticles for targeted delivery: Nanoparticles that react to environmental cues like pH, temperature, or bacterial enzymes are examples of recent developments. By enabling controlled, on-site medication release, these stimuli-responsive nanoparticles maximize antibacterial activity while reducing harm to healthy tissues ^[73].
Nanoparticle hydrogel composites: Metallic nanoparticles, such as AgNPs and ZnO NPs, can be incorporated into hydrogel systems to provide localized and long-lasting antibacterial activity. Research is being done on them for implant coatings, burn treatments, and wound dressings ^[74].
Green synthesis techniques: Eco-friendly techniques that employ microbes, plant extracts, or biopolymers are being developed to create nanoparticles that are more biocompatible and less harmful. This promotes sustainable nanomedicine and scalability ^[75].
Photothermal and photodynamic nanotherapy: In order to efficiently kill bacteria via non-antibiotic methods, gold nanoparticles, graphene-based materials, and quantum dots are being developed to transform light into heat or reactive oxygen species (ROS). This is especially helpful for infections caused by biofilms ^[76].
Nanoparticle loaded antibacterial coatings: Medical devices (such as orthopedic implants and catheters) now have antibacterial coatings because to developments in surface engineering. These coatings physically break down bacterial membranes by using nano-textured surfaces or by releasing antibacterial chemicals gradually ^[77].
Nanozymes (enzyme-mimetic nanoparticles): Nanozymes create ROS in bacterial settings by imitating natural enzymes. In order to combat resistant bacterial strains, they are being developed as non-toxic antibacterial agents having catalytic, self-renewing activity ^[78].
Combination therapies: The overall effectiveness is increased, dosage requirements are decreased, and the establishment of resistance is postponed when nanoparticles are combined with conventional antibiotics or natural antibacterial agents (such as essential oils or curcumin) ^[79].
Clinical trials and regulatory progress: A rising number of nanoparticle systems have entered or are approaching clinical review, including silver-based dressings, TiO?-coated devices, and antibiotics encapsulated in chitosan ^[80].

CONCLUSION

Nanoparticles (NPs) have become a promising class of antimicrobial drugs because of their distinct physicochemical characteristics and several modes of action, which include disrupting microbial membranes, producing reactive oxygen species (ROS), and interfering with the activities of proteins and DNA. Comparing these complex pathways to conventional antibiotics, the risk of resistance development is decreased. The design of intelligent, responsive, and targeted NP-based antimicrobial systems has been made possible by recent developments in nanotechnology, improving their efficacy and biocompatibility. Surface-functionalized NPs, hybrid nanomaterials, and stimuli-responsive drug delivery systems are examples of innovations that have greatly expanded the range of NP uses in industrial, environmental, and medical contexts. There are still issues with toxicity, stability, scalability, and regulatory approval in spite of these developments. To fully utilize nanoparticles' potential in addressing new infectious risks and fighting antibiotic resistance, more multidisciplinary research is required.

REFERENCES

Nasrollahzadeh M, Sajadi SM, Sajjadi M, Issaabadi Z. An introduction to nanotechnology. InInterface science and technology 2019 Jan 1 (Vol. 28, pp. 1-27). Elsevier.
Inshakova E, Inshakov O, Orlova A. Global and Russian nanotechnology product market development: comparison of trends and impact of sanctions. International Journal of Trade and Global Markets. 2017;10(2-3):226-35.
Parhizkar M, Mahalingam S, Homer-Vanniasinkam S, Edirisinghe M. Latest developments in innovative manufacturing to combine nanotechnology with healthcare. Nanomedicine. 2018 Jan;13(1):
Ghaedi M, Yousefinejad M, Safarpoor M, Khafri HZ, Purkait MK. Rosmarinus officinalis leaf extract mediated green synthesis of silver nanoparticles and investigation of its antimicrobial properties. Journal of Industrial and Engineering Chemistry. 2015 Nov 25;31:167-72.
Jackman JA, Cho DJ, Lee J, Chen JM, Besenbacher F, Bonnell DA, Hersam MC, Weiss PS, Cho NJ. Nanotechnology education for the global world: training the leaders of tomorrow.
Nikalje AP. Nanotechnology and its applications in medicine. Med chem. 2015 Mar;5(2):081-9.
Hulla JE, Sahu SC, Hayes AW. Nanotechnology: History and future. Human & experimental toxicology. 2015 Dec;34(12):1318-21.
GOLUBEV SS, SEKERIN VD, GOROKHOVA AE, GAYDUK NV. Nanotechnology market research: Development and prospects. Revista ESPACIOS. 2018 Sep 3;39(36).
Phan CM, Nguyen HM. Role of capping agent in wet synthesis of nanoparticles. The Journal of Physical Chemistry A. 2017 May 4;121(17):3213-9.
Al-Kattan A, Grojo D, Drouet C, Mouskeftaras A, Delaporte P, Casanova A, Robin JD, Magdinier F, Alloncle P, Constantinescu C, Motto-Ros V. Short-pulse lasers: a versatile tool in creating novel nano-/micro-structures and compositional analysis for healthcare and wellbeing challenges. Nanomaterials. 2021 Mar 12;11(3):712.
Rana S, Bhardwaj N, Singh V, Ashar MS. Approach of Computational study of Nanomaterials in Nanoinformatics.
Rane AV, Kanny K, Abitha VK, Thomas S. Methods for synthesis of nanoparticles and fabrication of nanocomposites. InSynthesis of inorganic nanomaterials 2018 Jan 1 (pp. 121-139). Woodhead publishing.
Thakur P, Thakur A. Introduction to nanotechnology. Synthesis and applications of nanoparticles. 2022 Jun 21:1-7.
Nabila MI, Kannabiran K. Biosynthesis, characterization and antibacterial activity of copper oxide nanoparticles (CuO NPs) from actinomycetes. Biocatalysis and agricultural biotechnology. 2018 Jul 1;15:56-62.
Roy P, Das B, Mohanty A, Mohapatra S. Green synthesis of silver nanoparticles using Azadirachta indica leaf extract and its antimicrobial study. Applied Nanoscience. 2017 Nov;7(8):843-5.
Ahmed KS, Hussein SA, Ali AH, Korma SA, Lipeng Q, Jinghua C. Liposome: Composition, characterisation, preparation, and recent innovation in clinical applications. Journal of drug targeting. 2019 Aug 9;27(7):742-61.
Panahi Y, Farshbaf M, Mohammadhosseini M, Mirahadi M, Khalilov R, Saghfi S, Akbarzadeh A. Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications. Artificial cells, nanomedicine, and biotechnology. 2017 May 19;45(4):788-99.
Krishnamoorthy K, Mahalingam M. Selection of a suitable method for the preparation of polymeric nanoparticles: multi-criteria decision making approach. Advanced pharmaceutical bulletin. 2015 Mar 5;5(1):57.
Cagel M, Tesan FC, Bernabeu E, Salgueiro MJ, Zubillaga MB, Moretton MA, Chiappetta DA. Polymeric mixed micelles as nanomedicines: Achievements and perspectives. European Journal of Pharmaceutics and Biopharmaceutics. 2017 Apr 1;113:211-28.
Gautam SP, Gupta AK, Gupta R, Gautam T, Singh MP. Dendrimers: a glimpse of history, current progress, and applications. Drug Delivery Approaches and Nanosystems, Volume 1. 2017 Nov 15:213-36.
Huang H, Feng W, Chen Y, Shi J. Inorganic nanoparticles in clinical trials and translations. Nano today. 2020 Dec 1;35:100972.
Mendes CR, Dilarri G, Forsan CF, Sapata VD, Lopes PR, de Moraes PB, Montagnolli RN, Ferreira H, Bidoia ED. Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens. Scientific reports. 2022 Feb 16;12(1):2658.
Meghana S, Kabra P, Chakraborty S, Padmavathy N. Understanding the pathway of antibacterial activity of copper oxide nanoparticles. RSC advances. 2015;5(16):12293-9.
Arakha M, Pal S, Samantarrai D, Panigrahi TK, Mallick BC, Pramanik K, Mallick B, Jha S. Antimicrobial activity of iron oxide nanoparticle upon modulation of nanoparticle-bacteria interface. Scientific reports. 2015 Oct 6;5(1):14813.
Gómez-Hernández R, Panecatl-Bernal Y, Méndez-Rojas MÁ. High yield and simple one-step production of carbon black nanoparticles from waste tires. Heliyon. 2019 Jul 1;5(7).
Pitkänen L, Striegel AM. Size-exclusion chromatography of metal nanoparticles and quantum dots. TrAC Trends in Analytical Chemistry. 2016 Jun 1;80:311-20.
Tulinski M, Jurczyk M. Nanomaterials synthesis methods. Metrology and standardization of nanotechnology: protocols and industrial innovations. 2017 Feb 15:75-98.
Nadaroglu H, Güngör AA, Ince S. Synthesis of nanoparticles by green synthesis method. International Journal of Innovative Research and Reviews. 2017 Aug;1(1):6-9.
Altammar KA. A review on nanoparticles: characteristics, synthesis, applications, and challenges. Frontiers in microbiology. 2023 Apr 17;14:1155622.
Sadoq BE, Britel MR, Bouajaj A, Maâlej R, Touhami A, Abid M, Douiri H, Touhami F, Maurady A. A review on antibacterial activity of nanoparticles. Biointerface Research in Applied Chemistry. 2023.
Sharmin S, Rahaman MM, Sarkar C, Atolani O, Islam MT, Adeyemi OS. Nanoparticles as antimicrobial and antiviral agents: A literature-based perspective study. Heliyon. 2021 Mar 1;7(3).
Feshchenko YI, Gumeniuk MI. Super-infections: does the humankind have weapons to fight?. Infusion & Chemotherapy. 2019 May 30(1):3-8.
Yusuf A, Almotairy AR, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: a review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers. 2023 Mar 23;15(7):1596.
Anand U, Carpena M, Kowalska-Góralska M, Garcia-Perez P, Sunita K, Bontempi E, Dey A, Prieto MA, Pro?ków J, Simal-Gandara J. Safer plant-based nanoparticles for combating antibiotic resistance in bacteria: A comprehensive review on its potential applications, recent advances, and future perspective. Science of The Total Environment. 2022 May 15;821:153472.
León-Buitimea A, Garza-Cárdenas CR, Garza-Cervantes JA, Lerma-Escalera JA, Morones-Ramírez JR. The demand for new antibiotics: antimicrobial peptides, nanoparticles, and combinatorial therapies as future strategies in antibacterial agent design. Frontiers in microbiology. 2020 Jul 24;11:1669.
Gupta D, Singh A, Khan AU. Nanoparticles as efflux pump and biofilm inhibitor to rejuvenate bactericidal effect of conventional antibiotics. Nanoscale research letters. 2017 Dec;12:1-6.
Xie M, Gao M, Yun Y, Malmsten M, Rotello VM, Zboril R, Akhavan O, Kraskouski A, Amalraj J, Cai X, Lu J. Antibacterial nanomaterials: mechanisms, impacts on antimicrobial resistance and design principles. Angewandte Chemie International Edition. 2023 Apr 17;62(17):e202217345.
Makabenta JM, Nabawy A, Li CH, Schmidt-Malan S, Patel R, Rotello VM. Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nature Reviews Microbiology. 2021 Jan;19(1):23-36.
Nisar P, Ali N, Rahman L, Ali M, Shinwari ZK. Antimicrobial activities of biologically synthesized metal nanoparticles: an insight into the mechanism of action. JBIC Journal of Biological Inorganic Chemistry. 2019 Oct;24:929-41.
Ahmed B, Hashmi A, Khan MS, Musarrat J. ROS mediated destruction of cell membrane, growth and biofilms of human bacterial pathogens by stable metallic AgNPs functionalized from bell pepper extract and quercetin. Advanced Powder Technology. 2018 Jul 1;29(7):1601-16.
Godoy-Gallardo M, Eckhard U, Delgado LM, de Roo Puente YJ, Hoyos-Nogués M, Gil FJ, Perez RA. Antibacterial approaches in tissue engineering using metal ions and nanoparticles: From mechanisms to applications. Bioactive Materials. 2021 Dec 1;6(12):4470-90.
Bhattacharya PK, Samnani PB. Metal ions in biochemistry. CRC press; 2020 Dec 13.
Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. International journal of nanomedicine. 2017 Feb 14:1227-49.
Xie W, Zhang S, Pan F, Chen S, Zhong L, Wang J, Pei X. Nanomaterial-based ROS-mediated strategies for combating bacteria and biofilms. Journal of Materials Research. 2021 Feb 28;36:822-45.
Tavares TD, Antunes JC, Padrão J, Ribeiro AI, Zille A, Amorim MT, Ferreira F, Felgueiras HP. Activity of specialized biomolecules against gram-positive and gram-negative bacteria. Antibiotics. 2020 Jun 9;9(6):314.
Adeniji OO, Nontongana N, Okoh JC, Okoh AI. The potential of antibiotics and nanomaterial combinations as therapeutic strategies in the management of multidrug-resistant infections: a review. International journal of molecular sciences. 2022 Nov 30;23(23):15038.
Gupta A, Saleh NM, Das R, Landis RF, Bigdeli A, Motamedchaboki K, Campos AR, Pomeroy K, Mahmoudi M, Rotello VM. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection. Nano Futures. 2017 May 2;1(1):015004.
Rudramurthy GR, Swamy MK, Sinniah UR, Ghasemzadeh A. Nanoparticles: alternatives against drug-resistant pathogenic microbes. Molecules. 2016 Jun 27;21(7):836.
Mamun MM, Sorinolu AJ, Munir M, Vejerano EP. Nanoantibiotics: Functions and properties at the nanoscale to combat antibiotic resistance. Frontiers in chemistry. 2021 May 13;9:687660.
Hetta HF, Ramadan YN, Al-Harbi AI, A. Ahmed E, Battah B, Abd Ellah NH, Zanetti S, Donadu MG. Nanotechnology as a promising approach to combat multidrug resistant bacteria: a comprehensive review and future perspectives. Biomedicines. 2023 Jan 31;11(2):413.
Ozdal M, Gurkok S. Recent advances in nanoparticles as antibacterial agent. ADMET and DMPK. 2022 Mar 4;10(2):115-29.
Abdullah, Jamil T, Atif M, Khalid S, Metwally K, Yahya G, Moisa M, Cavalu DS. Recent Advances in the Development of Metal/Metal Oxide Nanoparticle and Antibiotic Conjugates (MNP–Antibiotics) to Address Antibiotic Resistance: Review and Perspective. International Journal of Molecular Sciences. 2024 Aug 16;25(16):8915.
Saker R, Regdon jr G, Sovány T. Pharmacokinetics and toxicity of inorganic nanoparticles and the physicochemical properties/factors affecting them. Journal of Drug Delivery Science and Technology. 2024 Jul 15:105979.
Ferdous Z, Nemmar A. Health impact of silver nanoparticles: a review of the biodistribution and toxicity following various routes of exposure. International journal of molecular sciences. 2020 Mar 30;21(7):2375.
Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020 May 8;25(9):2193.
Malik S, Muhammad K, Waheed Y. Nanotechnology: a revolution in modern industry. Molecules. 2023 Jan 9;28(2):661.
Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale research letters. 2018 Dec;13:1-21.
Zhang XF, Shen W, Gurunathan S. Silver nanoparticle-mediated cellular responses in various cell lines: an in vitro model. International journal of molecular sciences. 2016 Sep 22;17(10):1603.
Sajid M, Ilyas M, Basheer C, Tariq M, Daud M, Baig N, Shehzad F. Impact of nanoparticles on human and environment: review of toxicity factors, exposures, control strategies, and future prospects. Environmental Science and Pollution Research. 2015 Mar;22:4122-43.
Tang Y, Liu B, Zhang Y, Liu Y, Huang Y, Fan W. Interactions between nanoparticles and lymphatic systems: mechanisms and applications in drug delivery. Advanced Drug Delivery Reviews. 2024 Apr 9:115304.
Bakand S, Hayes A. Toxicological considerations, toxicity assessment, and risk management of inhaled nanoparticles. International journal of molecular sciences. 2016 Jun 14;17(6):929.
Xu L, Dan M, Shao A, Cheng X, Zhang C, Yokel RA, Takemura T, Hanagata N, Niwa M, Watanabe D. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model. International journal of nanomedicine. 2015 Sep 29:6105-19.
Liu X, Sui B, Sun J. Blood-brain barrier dysfunction induced by silica NPs in vitro and in vivo: Involvement of oxidative stress and Rho-kinase/JNK signaling pathways. Biomaterials. 2017 Mar 1;121:64-82.
Bendale Y, Bendale V, Paul S. Evaluation of cytotoxic activity of platinum nanoparticles against normal and cancer cells and its anticancer potential through induction of apoptosis. Integrative medicine research. 2017 Jun 1;6(2):141-8.
Liu N, Tang M. Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles. Journal of Applied Toxicology. 2020 Jan;40(1):16-36.
Greening C, Lithgow T. Formation and function of bacterial organelles. Nature Reviews Microbiology. 2020 Dec;18(12):677-89.
Mazaheri N, Naghsh N, Karimi A, Salavati H. In vivo toxicity investigation of magnesium oxide nanoparticles in rat for environmental and biomedical applications. Iranian journal of biotechnology. 2019 Jan 11;17(1):e1543.
Setudeh F, Arabi M. Oxidative Stress Biomarkers in Hepatic and Cardiac Toxicity Induced by Copper Oxide Nanoparticles in Mice. Journal of Chemical Health Risks. 2024 Dec 1;14(4).
Wu T, Tang M. The inflammatory response to silver and titanium dioxide nanoparticles in the central nervous system. Nanomedicine. 2018 Jan 1;13(2):233-49.
Damle A, Sundaresan R, Rajwade JM, Srivastava P, Naik A. A concise review on implications of silver nanoparticles in bone tissue engineering. Biomaterials Advances. 2022 Oct 1;141:213099.
Fatima F, Siddiqui S, Khan WA. Nanoparticles as novel emerging therapeutic antibacterial agents in the antibiotics resistant era. Biological Trace Element Research. 2021 Jul;199(7):2552-64.
Najahi-Missaoui W, Arnold RD, Cummings BS. Safe nanoparticles: are we there yet?. International journal of molecular sciences. 2020 Dec 31;22(1):385.
Qu M, Jiang X, Zhou X, Wang C, Wu Q, Ren L, Zhu J, Zhu S, Tebon P, Sun W, Khademhosseini A. Stimuli?responsive delivery of growth factors for tissue engineering. Advanced healthcare materials. 2020 Apr;9(7):1901714.
Ahmadian Z, Gheybi H, Adeli M. Efficient wound healing by antibacterial property: Advances and trends of hydrogels, hydrogel-metal NP composites and photothermal therapy platforms. Journal of Drug Delivery Science and Technology. 2022 Jul 1;73:103458.
Bhardwaj B, Singh P, Kumar A, Kumar S, Budhwar V. Eco-friendly greener synthesis of nanoparticles. Advanced pharmaceutical bulletin. 2020 Aug 9;10(4):566.
Kumari R, Sunil D. Emerging trends in aggregation induced emissive luminogens as bacterial theranostics. Journal of Drug Targeting. 2021 Sep 14;29(8):793-807.
Malhotra A, Mutton G, Chauhan SR, Semetey V, Chauhan A. Chap 26: Medical Device Associated-Biofilm Eradication Strategies: Use of Multi-Functional Nanomaterials. In: Sabu Thomas, Nandakumar Kalarikkal, Dr. Ann Rose Abraham (eds) Applications of Multifunctional Nanomaterials. Elsevier. Chap 26: Medical Device Associated-Biofilm Eradication Strategies: Use of Multi-Functional Nanomaterials. In: Sabu Thomas, Nandakumar Kalarikkal, Dr. Ann Rose Abraham (eds) Applications of Multifunctional Nanomaterials. Elsevier.. 2023 Mar 30.
Liu K, Xue Z, Feng T, Dou X, Sipaut CS, Yuan X. Ultrasmall coinage metal nanoclusters as promising antibacterial agents: from design to applications. Chemical Communications. 2025.
Trifan A, Luca SV, Greige-Gerges H, Miron A, Gille E, Aprotosoaie AC. Recent advances in tackling microbial multidrug resistance with essential oils: Combinatorial and nano-based strategies. Critical Reviews in Microbiology. 2020 May 3;46(3):338-57.
Ragelle H, Danhier F, Préat V, Langer R, Anderson DG. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Expert opinion on drug delivery. 2017 Jul 3;14(7):851-64.