Antibiotic Alternatives: Multifunctional Ultra-Small Metal Nanoclusters for Bacterial Infectious Therapy Application.

The prevalence of major bacterial infections has emerged as a significant menace to human health and life. Conventional treatment methods primarily rely on antibiotic therapy, but the overuse of these drugs has led to a decline in their efficacy. Moreover, bacteria have developed resistance towards antibiotics, giving rise to the emergence of superbugs. Consequently, there is an urgent need for novel antibacterial agents or alternative strategies to combat bacterial infections. Nanoantibiotics encompass a class of nano-antibacterial materials that possess inherent antimicrobial activity or can serve as carriers to enhance drug delivery efficiency and safety. In recent years, metal nanoclusters (M NCs) have gained prominence in the field of nanoantibiotics due to their ultra-small size (less than 3 nm) and distinctive electronic and optical properties, as well as their biosafety features. In this review, we discuss the recent progress of M NCs as a new generation of antibacterial agents. First, the main synthesis methods and characteristics of M NCs are presented. Then, we focus on reviewing various strategies for detecting and treating pathogenic bacterial infections using M NCs, summarizing the antibacterial effects of these nanoantibiotics on wound infections, biofilms, and oral infections. Finally, we propose a perspective on the remaining challenges and future developments of M NCs for bacterial infectious therapy.

Fighting Methicillin-Resistant Staphylococcus aureus with Targeted Nanoparticles.

Antimicrobial resistance (AMR) is considered one of the greatest threats to global health. Methicillin-resistant Staphylococcus aureus (MRSA) remains at the core of this threat, accounting for about 90% of S. aureus infections widespread in the community and hospital settings. In recent years, the use of nanoparticles (NPs) has emerged as a promising strategy to treat MRSA infections. NPs can act directly as antibacterial agents via antibiotic-independent activity and/or serve as drug delivery systems (DDSs), releasing loaded antibiotics. Nonetheless, directing NPs to the infection site is fundamental for effective MRSA treatment so that highly concentrated therapeutic agents are delivered to the infection site while directly reducing the toxicity to healthy human cells. This leads to decreased AMR emergence and less disturbance of the individual's healthy microbiota. Hence, this review compiles and discusses the scientific evidence related to targeted NPs developed for MRSA treatment.

Antibacterial metal nanoclusters.

Combating bacterial infections is one of the most important applications of nanomedicine. In the past two decades, significant efforts have been committed to tune physicochemical properties of nanomaterials for the development of various novel nanoantibiotics. Among which, metal nanoclusters (NCs) with well-defined ultrasmall size and adjustable surface chemistry are emerging as the next-generation high performance nanoantibiotics. Metal NCs can penetrate bacterial cell envelope more easily than conventional nanomaterials due to their ultrasmall size. Meanwhile, the abundant active sites of the metal NCs help to catalyze the bacterial intracellular biochemical processes, resulting in enhanced antibacterial properties. In this review, we discuss the recent developments in metal NCs as a new generation of antimicrobial agents. Based on a brief introduction to the characteristics of metal NCs, we highlight the general working mechanisms by which metal NCs combating the bacterial infections. We also emphasize central roles of core size, element composition, oxidation state, and surface chemistry of metal NCs in their antimicrobial efficacy. Finally, we present a perspective on the remaining challenges and future developments of metal NCs for antibacterial therapeutics.

SnO2nanorods/graphene nanoplatelets nanocomposites: towards fast removal of malachite green and pathogen control.

The world is facing alarming challenges of environmental pollution due to uncontrolled water contamination and multiple drug resistance of pathogens. However, these challenges can be addressed by using novel nanocomposites materials such as, SnO2/graphene nanopaletelets (GNPs) nanocomposites remarkably. In this work, we have prepared SnO2nanorods and SnO2/GNPs nanocomposites (GS-I and GS-II) with size of 25 ± 6 nm in length and 4 ± 2 nm in diameter. The optical bandgap energies change from 3.14 eV to 2.80 eV in SnO2and SnO2/GNPs nanocomposite. We found that SnO2/GNPs nanocomposite (GS-II) completely removes (99.11%) malachite green in 12 min, under UV light exposure, while under same conditions, SnO2nanorods removes only 37% dye. Moreover, visible light exposure resulted in 99.01% removal of malachite green in 15 min by GSII as compared to 24.7% removal by SnO2. In addition, GS-II nanocomposite inhibits 79.57% and 78.51% growth ofP. aeruginosaandS. aureusrespectively. A synchronized contribution of SnO2and GNPs makes SnO2/GNPs nanocomposites (GS-II) an innovative multifunctional material for simultaneous fast and complete removal of malachite green and inhibition of drug resistant pathogens.

Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria.

Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections. This is a menace where conventional chemotherapies are no longer promising, but several novel approaches could help. Our current review article discusses the novel approaches that can combat MDR bacteria: starting off with potential nanoparticles (NPs) that efficiently interact with microorganisms causing fatal changes in the morphology and structure of these cells; nanophotothermal therapy using inorganic NPs like AuNPs to destroy pathogenic bacterial cells; bacteriophage therapy against which bacteria develop less resistance; combination drugs that act on dissimilar targets in distinctive pathways; probiotics therapy by the secretion of antibacterial chemicals; blockage of quorum sensing signals stopping bacterial colonization, and vaccination against resistant bacterial strains along with virulence factors. All these techniques show us a promising future in the fight against MDR bacteria, which remains the greatest challenge in public health care.

Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: current status and potential future applications.

Nanotechnology-based therapeutic approaches have attracted attention of scientists, in particular due to the special features of nanomaterials, such as adequate biocompatibility, ability to improve therapeutic efficiency of incorporated drugs and to limit their adverse effects. Among a variety of reported nanomaterials for biomedical applications, metal and metal oxide-based nanoparticles offer unique physicochemical properties allowing their use in combination with conventional antimicrobials and as magnetic field-controlled drug delivery nanocarriers. An ever-growing number of studies demonstrate that by combining magnetic nanoparticles with membrane-active, natural human cathelicidin-derived LL-37 peptide, and its synthetic mimics such as ceragenins, innovative nanoagents might be developed. Between others, they demonstrate high clinical potential as antimicrobial, anti-cancer, immunomodulatory and regenerative agents. Due to continuous research, knowledge on pleiotropic character of natural antibacterial peptides and their mimics is growing, and it is justifying to stay that the therapeutic potential of nanosystems containing membrane active compounds has not been exhausted yet.

Prospects and application of nanobiotechnology in food preservation: molecular perspectives.

Applications of biotechnological tools in food preservation have shown promising results in minimizing food spoilage. Design and development of highly efficient food preservatives are one of the key success factors in this application field. However, due to the inherent shortcomings of the bulk forms of such preservatives, research was in progress to find suitable alternatives to replace conventional modalities. The intervention of nanotechnology has made this approach feasible in almost every aspect of food preservation. This interface domain of nanobiotechnology has been very well explored in the last few decades and vast literature has been reported. Researchers have developed efficient nanopreservatives (NPRs) for diverse applications. However, the literature available on nano-based food preservation is not inclusive of molecular perspectives involved in food preservation. There is a large knowledge gap in the interface domain concerning the physics of intermolecular and interfacial forces and nanotechnology which play decisive roles in designing edible coatings (ECs). There is an urgent need for identifying the nano and molecular level contributing factors for developing efficient NPRs. Moreover, it is imperative to understand the possible health impact of NPRs in public interest and concern. This review revisits the fundamental aspects of food preservation and navigates through the applicability, safety, molecular aspects and future direction of NPRs.

Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles.

Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a number of future prospects.

Factors pivotal for designing of nanoantimicrobials: an exposition.

Understanding the interplay between bacterial pathogens and antimicrobials is a key to realize the control over infections causing morbidity and mortality. An important current issue of contemporary medicine and microbiology is the search for new strategies for adequate therapy of infectious diseases associated with rapidly emerging multidrug-resistant (MDR) pathogens. Recently, a great deal of progress has been made in the field of nanobiotechnology towards the development of various nanoantimicrobials (NAMs) as novel therapeutic solution. Current microbiological studies, employing either synthetic antibiotics or natural antimicrobial, have demonstrated the ability of NAMs to tackle the issue of MDR by reverting the mechanisms of resistance. The present review critically discusses the various factors that can contribute to modulate the effects of NAMs on microbes. It includes essential features of NAMs including but not limited to composition, surface charge, loading capacity, size, hydrophobicity/philicity, controlled release and functionalization. In contrast, how microbial structural differences, biofilm formation, persister cells and intracellular pathogens contribute towards sensitivity or resistance towards antimicrobials is comprehensively analysed. These multilateral factors should be considered earnestly in order to make NAMs a successful alternative of the conventional antibiotics.

N-Heterocycle Modified Graphene Quantum Dots as Topoisomerase Targeted Nanoantibiotics for Combating Microbial Infections.

Developing next-generation antibiotics to eliminate multidrug-resistant (MDR) bacteria/fungi and stubborn biofilms is challenging, because of the excessive use of currently available antibiotics. Herein, the fabrication of anti-infection graphene quantum dots (GQDs) is reported, as a new class of topoisomerase (Topo) targeting nanoantibiotics, by modification of rich N-heterocycles (pyridinic N) at edge sites. The membrane-penetrating, nucleus-localizing, DNA-binding GQDs not only damage the cell walls/membranes of bacteria or fungi, but also inhibit DNA-binding proteins, such as Topo I, thereby affecting DNA replication, transcription, and recombination. The obtained GQDs exhibit excellent broad-spectrum antimicrobial activity against non-MDR bacteria, MDR bacteria, endospores, and fungi. Beyond combating planktonic microorganisms, GQDs inhibit the formation of biofilms and can kill live bacteria inside biofilms. RNA-seq further demonstrates the upregulation of riboflavin biosynthesis genes, DNA repair related genes, and transport proteins related genes in methicillin-resistant S. aureus (MRSA) in response to the stress induced by GQDs. In vivo animal experiments indicate that the biocompatible GQDs promote wound healing in MRSA or C. albicans-infected skin wound models. Thus, GQDs may be a promising antibacterial and antifungal candidate for clinical applications in treating infected wounds and eliminating already-formed biofilms.

Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity.

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Narrow spectrum nano-antibiotic for selective removal of ARB from contaminated water: New insights into stimuli response based on cellular attachment, lysis, and excretion.

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer-inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.

A ruthenium single atom nanozyme-based antibiotic for the treatment of otitis media caused by Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 demonstrates the optimal peroxidase-like activity (285.3 U mg-1), comparable to that of horseradish peroxidase (267.7 U mg-1). In vitro antibacterial assays reveal that Ru-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06 mg mL-1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C3N4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus-induced OM.

Host immunomodulation strategies to combat pandemic-associated antimicrobial-resistant secondary bacterial infections.

The incidence of secondary bacterial infections has increased in recent decades owing to various viral pandemics. These infections further increase the morbidity and mortality rates associated with viral infections and remain a significant challenge in clinical practice. Intensive antibiotic therapy has mitigated the threat of such infections; however, overuse and misuse of antibiotics have resulted in poor outcomes, such as inducing the emergence of bacterial populations with antimicrobial resistance (AMR) and reducing the therapeutic options for this crisis. Several antibiotic substitutes have been suggested and employed; however, they have certain limitations and novel alternatives are urgently required. This review highlights host immunomodulation as a promising strategy against secondary bacterial infections to overcome AMR. The definition and risk factors of secondary bacterial infections, features and limitations of currently available therapeutic strategies, host immune responses, and future perspectives for treating such infections are discussed.

Minimum Information for Conducting and Reporting In Vitro Intracellular Infection Assays.

Bacterial pathogens are constantly evolving to outsmart the host immune system and antibiotics developed to eradicate them. One key strategy involves the ability of bacteria to survive and replicate within host cells, thereby causing intracellular infections. To address this unmet clinical need, researchers are adopting new approaches, such as the development of novel molecules that can penetrate host cells, thus exerting their antimicrobial activity intracellularly, or repurposing existing antibiotics using nanocarriers (i.e., nanoantibiotics) for site-specific delivery. However, inconsistency in information reported across published studies makes it challenging for scientific comparison and judgment of experiments for future direction by researchers. Together with the lack of reproducibility of experiments, these inconsistencies limit the translation of experimental results beyond pre-clinical evaluation. Minimum information guidelines have been instrumental in addressing such challenges in other fields of biomedical research. Guidelines and recommendations provided herein have been designed for researchers as essential parameters to be disclosed when publishing their methodology and results, divided into four main categories: (i) experimental design, (ii) establishing an in vitro model, (iii) assessment of efficacy of novel therapeutics, and (iv) statistical assessment. These guidelines have been designed with the intention to improve the reproducibility and rigor of future studies while enabling quantitative comparisons of published studies, ultimately facilitating translation of emerging antimicrobial technologies into clinically viable therapies that safely and effectively treat intracellular infections.

Combinational antimicrobial activity of biogenic TiO2 NP/ZnO NPs nanoantibiotics and amoxicillin-clavulanic acid against MDR-pathogens.

The development of effective strategies against multidrug-resistant (MDR) pathogens is an urgent need in modern medicine. Nanoantibiotics (nABs) offer a new hope in countering the surge of MDR-pathogens. The aim of the current study was to evaluate the antibacterial activity of two attractive nABs, TiO2 NPs and ZnO NPs, and their performance in improving the antimicrobial activity of defined antibiotics (amoxicillin-clavulanic acid, amox-clav) against MDR-pathogens. The nABs were synthesized using a green method. The physicochemical characteristics of the synthesized nanoparticles were determined using standard methods. The results showed the formation of pure anatase TiO2 NPs and hexagonal ZnO NPs with an average particle size of 38.65 nm and 57.87 nm, respectively. The values of zeta potential indicated the high stability of the samples. At 8 mg/mL, both nABs exhibited 100 % antioxidant activity, while ZnO showed significantly higher activity at lower concentrations. The antibiofilm assay showed that both nABs could inhibit the formation of biofilms of Acinetobacter baumannii 80 and Escherichia coli 27G (MDR-isolates). However, ZnO NPs showed superior antibiofilm activity (100 %) against E. coli 27G. The MIC values were determined to be 8 (1), 2 (2), and 4 (4) mg/mL for amox-clav, TiO2 NPs, and ZnO NPs against A. baumannii 80 (E. coli 27G), respectively. The results showed that both nABs had synergistically enhanced antibacterial performance in combination with amox-clav. Specifically, an 8-fold reduction in MIC values of antibiotics was observed when they were combined with nABs. These findings highlight the potential of TiO2 NPs and ZnO NPs as effective nanoantibiotics against MDR-pathogens. The synergistic effect observed when combining nABs with antibiotics suggests a promising approach for combating antibiotic resistance. Further research and development in this area could lead to the development of more effective treatment strategies against MDR infections.

Zinc oxide nanoparticles mediate bacterial toxicity in Mueller-Hinton Broth via Zn2.

As antibiotic resistance increases and antibiotic development dwindles, new antimicrobial agents are needed. Recent advances in nanoscale engineering have increased interest in metal oxide nanoparticles, particularly zinc oxide nanoparticles, as antimicrobial agents. Zinc oxide nanoparticles are promising due to their broad-spectrum antibacterial activity and low production cost. Despite many studies demonstrating the effectiveness of zinc oxide nanoparticles, the antibacterial mechanism is still unknown. Previous work has implicated the role of reactive oxygen species such as hydrogen peroxide, physical damage of the cell envelope, and/or release of toxic Zn2+ ions as possible mechanisms of action. To evaluate the role of these proposed methods, we assessed the susceptibility of S. aureus mutant strains, ΔkatA and ΔmprF, to zinc oxide nanoparticles of approximately 50 nm in size. These assays demonstrated that hydrogen peroxide and electrostatic interactions are not crucial for mediating zinc oxide nanoparticle toxicity. Instead, we found that Zn2+ accumulates in Mueller-Hinton Broth over time and that removal of Zn2+ through chelation reverses this toxicity. Furthermore, we found that the physical separation of zinc oxide nanoparticles and bacterial cells using a semi-permeable membrane still allows for growth inhibition. We concluded that soluble Zn2+ is the primary mechanism by which zinc oxide nanoparticles mediate toxicity in Mueller-Hinton Broth. Future work investigating how factors such as particle morphology (e.g., size, polarity, surface defects) and media contribute to Zn2+ dissolution could allow for the synthesis of zinc oxide nanoparticles that possess chemical and morphological properties best suited for antibacterial efficacy.

Antibacterial efficacy, mode of action, and safety of a novel nano-antibiotic against antibiotic-resistant Escherichia coli strains.

Globally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to treatment failure with current antibiotics. Enterobacteria, particularly Escherichia coli, cause infections of surgical wound, bloodstream, and urinary tract, including pneumonia and sepsis. Herein, we tested in vitro antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH2-AgNP) against the AR bacteria. Two AR E. coli strains (i.e., ampicillin- and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5α, were tested for susceptibility to NH2-AgNP using Kirby-Bauer disk diffusion and standard growth assays. Dynamic light scattering (DLS) was used to determine cell debris and relative conductance was used as a measure of cell leakage, and results were confirmed with transmission electron microscopy (TEM). Multiple oxidative stress assays were used for in vitro safety evaluation of NH2-AgNP in human lung epithelial cells. Results showed that ampicillin and kanamycin did not inhibit growth in either AR bacterial strain with doses up to 160 µg/mL tested. NH2-AgNP exhibited broad-spectrum bactericidal activity, inhibiting the growth of all three bacterial strains at doses ≥1 µg/mL. DLS and TEM revealed cell debris formation and cell leakage upon NH2-AgNP treatment, suggesting two possible MoAs: electrostatic interactions followed by cell wall damage. Safety evaluation revealed NH2-AgNP as noncytotoxic and antioxidative to human lung epithelial cells. Taken together, these results suggest that NH2-AgNP may serve as an effective and safer bactericidal therapy against AR bacterial infections compared to common antibiotics.

Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives.

The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.

Harnessing the power of PLA-PEG nanoparticles for Linezolid delivery against methicillin-resistant Staphylococcus aureus.

This study deals with the development of novel poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) for the efficient and prolonged delivery of Linezolid (LNZ), a synthetic antibacterial agent used against methicillin-resistant Staphylococcus aureus (MRSA). A two-step synthetic strategy based on carbodiimide coupling and copper-catalyzed azide-alkyne cycloaddition was first exploited for the conjugation of PLA with PEG. The encapsulation of LNZ into medium-molecular-weight PLA-PEG NPs was carried out by different methods including nanoprecipitation and dialysis. The optimal PLA-PEG@LNZ nanoformulation resulted in 3.5% LNZ payload (15% encapsulation efficiency, with a 10:3 polymer to drug mass ratio) and sustained release kinetics with 65% of entrapped antibiotic released within 80 h. Moreover, the zeta potential values (from -31 to -39 mV) indicated a good stability without agglomeration even after freeze-drying and lyophilization. The PLA-PEG@LNZ NPs exerted antimicrobial activity against a panel of Gram-positive bacteria responsible for human infections, such as Staphylococcus aureus including MRSA, Staphylococcus epidermidis, Staphylococcus lugdunensis and vancomycin-resistant Enterococcus faecium (VREfm). Moreover, PLA-PEG@LNZ NPs showed inhibitory activity on both planktonic growth and preformed biofilm of MRSA. The antibacterial activity of LNZ incorporated in polymeric NPs was well preserved and the nanosystem served as an antibiotic enhancer with a potential role in MRSA-associated infections management.