Integrative analysis discovers Imidurea as dual multitargeted inhibitor of CD69, CD40, SHP2, lysozyme, GATA3, cCBL, and S-cysteinase from SARS-CoV-2 and M. tuberculosis.

Two of the deadliest infectious diseases, COVID-19 and tuberculosis (TB), have combined to establish a worldwide pandemic, wreaking havoc on economies and claiming countless lives. The optimised, multitargeted medications may diminish resistance and counter them together. Based on computational expression studies, 183 genes were co-expressed in COVID-19 and TB blood samples. We used the multisampling screening algorithms on the top ten co-expressed genes (CD40, SHP2, Lysozyme, GATA3, cCBL, SIVmac239 Nef, CD69, S-adenosylhomocysteinase, Chemokine Receptor-7, and Membrane Protein). Imidurea is a multitargeted inhibitor for COVID-19 and TB, as confirmed by extensive screening and post-filtering utilising MM\GBSA algorithms. Imidurea has shown docking and MM\GBSA scores of -8.21 to -4.75 Kcal/mol and -64.16 to -29.38 Kcal/mol, respectively. The DFT, pharmacokinetics, and interaction patterns suggest that Imidurea may be a drug candidate, and all ten complexes were tested for stability and bond strength using 100 ns for all MD atoms. The modelling findings showed the complex's repurposing potential, with a cumulative deviation and fluctuation of <2 Å and significant intermolecular interaction, which validated the possibilities. Finally, an inhibition test was performed to confirm our in-silico findings on SARS-CoV-2 Delta variant infection, which was suppressed by adding imidurea to Vero E6 cells after infection.

Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

BACKGROUND: In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments. OBJECTIVES: Present manuscript describes antifungal activity of an indole derivative 1-(4-((5- methoxy-2-(3,4,5-trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS- Delhi). METHODS: The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5- trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity. RESULTS: Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 µg/mL to 250 µg/mL and MFC values between 62.5 µg/mL to 500 µg/mL. In checkerboard assay synergistic mode of interaction of 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic. CONCLUSION: In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations.

Unveiling the cytotoxic and anti-proliferative potential of green-synthesized silver nanoparticles mediated by Colletotrichum gloeosporioides.

Fungal endophytes are a putative source of bioactive metabolites that have found significant applications in nanomedicine due to their metabolic versatility. In the present study, an aqueous extract of the fungal endophyte, Colletotrichum gloeosporioides associated with a medicinal plant Oroxylum indicum, has been used for the fabrication of green silver nanoparticles (CgAgNPs) and further evaluated their cytotoxic and anti-proliferative activity. Bioanalytical techniques including UV-Vis spectral analysis revealed a sharp band at 435 nm and functional molecules from the aqueous extract involved in the synthesis of CgAgNPs were evidenced through FTIR. Further, the crystalline nature of CgAgNPs was determined through XRD analysis and microscopy techniques including AFM, TEM and FESEM demonstrated the spherical shape of CgAgNPs exhibiting a crystalline hexagonal lattice and the size was found to be in the range of 9-29 nm. The significant cytotoxic potential of CgAgNPs was observed against breast cancer cells, MDA-MB-231 and MCF-7 with IC50 values of 18.398 ± 0.376 and 38.587 ± 1.828 µg mL-1, respectively. The biochemical study revealed that the treatment of MDA-MB-231 and MCF-7 cells with CgAgNPs reduces glucose uptake, suppresses cell proliferation, and enhances LDH release, indicating reduced cell viability and progression. Moreover, our research revealed differential expression of genes associated with apoptosis, cell cycle inhibition and metastasis suppression, evidencing anti-proliferative activity of CgAgNPs. The main objective of the present study is to harness anti-breast cancer activity of novel biogenic nanoparticles synthesized using the aqueous extract of O. indicum associated C. gloeosporioides and study the underlying mechanistic pathway exerted by these mycogenic nanoparticles.

Multisampling-based docking reveals Imidazolidinyl urea as a multitargeted inhibitor for lung cancer: an optimisation followed multi-simulation and in-vitro study.

Lung Cancer is one of the deadliest cancers, responsible for more than 1.80 million deaths annually worldwide, and it is on the priority list of WHO. In the current scenario, when cancer cells become resistant to the drug, making it less effective leaves the patient in vulnerable conditions. To overcome this situation, researchers are constantly working on new drugs and medications that can help fight drug resistance and improve patients' outcomes. In this study, we have taken five main proteins of lung cancer, namely RSK4 N-terminal kinase, guanylate kinase, cyclin-dependent kinase 2, kinase CK2 holoenzyme, tumour necrosis factor-alpha and screened the prepared Drug Bank library with 1,55,888 compounds against all using three Glide-based docking algorithms namely HTVS, standard precision and extra precise with a docking score ranging from -5.422 to -8.432 Kcal/mol. The poses were filtered with the MM\GBSA calculations, which helped to identify Imidazolidinyl urea C11H16N8O8 (DB14075) as a multitargeted inhibitor for lung cancer, validated with advanced computations like ADMET, interaction pattern fingerprints, and optimised the compound with Jaguar, producing satisfied relative energy. All five complexes were performed with MD Simulation for 100 ns with NPT ensemble class, producing cumulative deviation and fluctuations < 2 Å and a web of intermolecular interaction, making the complexes stable. Further, the in-vitro analysis for morphological imaging, Annexin V/PI FACS assay, ROS and MMP analysis caspase3//7 activity were performed on the A549 cell line producing promising results and can be an option to treat lung cancer at a significantly cheaper state.Communicated by Ramaswamy H. Sarma.

White-Light-Responsive Prussian Blue Nanophotonic Particles for Effective Eradication of Bacteria and Improved Healing of Infected Cutaneous Wounds.

The increasing burden of cutaneous wound infections with drug-resistant bacteria underlines the dire need for novel treatment approaches. Here, we report the preparation steps, characterization, and antibacterial efficacy of novel chitosan-coated Prussian blue nanoparticles loaded with the photosensitizer fluorescein isothiocyanate-dextran (CHPB-FD). With excellent photothermal and photodynamic properties, CHPB-FD nanoparticles can effectively eradicate both Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa in vitro and in vivo. The antibacterial efficacy of CHPB-FD nanophotonic particles further increases in the presence of white light. Using a bacteria-infected cutaneous wound rat model, we demonstrate that CHPB-FD particles upregulate genes involved in tissue remodeling, promote collagen deposition, reduce unwanted inflammation, and enhance healing. The light-responsive CHPB-FD nanophotonic particles can, therefore, be potentially used as an economical and safe alternative to antibiotics for effectively decontaminating skin wounds and for disinfecting biomedical equipment and surfaces in hospitals and other places.

The role of plant growth promoting rhizobacteria in strengthening plant resistance to fluoride toxicity: a review.

A wide variety of bacteria are present in soil but in rhizospheric area, the majority of microbes helps plant in defending diseases and facilitate nutrient uptake. These microorganisms are supported by plants and they are known as plant growth-promoting rhizobacteria (PGPR). The PGPRs have the potential to replace chemical fertilizers in a way that is more advantageous for the environment. Fluoride (F) is one of the highly escalating, naturally present contaminants that can be hazardous for PGPRs because of its antibacterial capacity. The interactions of F with different bacterial species in groundwater systems are still not well understood. However, the interaction of PGPR with plants in the rhizosphere region reduces the detrimental effects of pollutants and increases plants' ability to endure abiotic stress. Many studies reveal that PGPRs have developed F defense mechanisms, which include efflux pumps, Intracellular sequestration, enzyme modifications, enhanced DNA repair mechanism, detoxification enzymes, ion transporter/antiporters, F riboswitches, and genetic mutations. These resistance characteristics are frequently discovered by isolating PGPRs from high F-contaminated areas or by exposing cells to fluoride in laboratory conditions. Numerous studies have identified F-resistant microorganisms that possess additional F transporters and duplicates of the well-known targets of F. Plants are prone to F accumulation despite the soil's low F content, which may negatively affect their growth and development. PGPRs can be used as efficient F bioremediators for the soil environment. Environmental biotechnology focuses on creating genetically modified rhizobacteria that can degrade F contaminants over time. The present review focuses on a thorough systemic analysis of contemporary biotechnological techniques, such as gene editing and manipulation methods, for improving plant-microbe interactions for F remediation and suggests the importance of PGPRs in improving soil health and reducing the detrimental effects of F toxicity. The most recent developments in the realm of microbial assistance in the treatment of F-contaminated environments are also highlighted.

Computational screening and MM/GBSA-based MD simulation studies reveal the high binding potential of FDA-approved drugs against Cutibacterium acnes sialidase.

Cutibacterium acnes is an opportunistic pathogen linked with acne vulgaris, affecting 80-90% of teenagers globally. On the leukocyte (WBCs) cell surface, the cell wall anchored sialidase in C. acnes virulence factor, catalysing the sialoconjugates into sialic acids and nutrients for C. acnes resulting in human skin inflammation. The clinical use of antibiotics for acne treatments has severe adverse effects, including microbial dysbiosis and resistance. Therefore, identifying inhibitors for primary virulence factors (Sialidase) was done using molecular docking of 1030 FDA-approved drugs. Initially, based on binding energies (ΔG), Naloxone (ZINC000000389747), Fenoldopam (ZINC000022116608), Labetalol (ZINC000000403010) and Thalitone (ZINC000000057255) were identified that showed high binding energies as -10.2, -10.1, -9.9 and -9.8 kcal/mol, respectively. In 2D analysis, these drugs also showed considerable structural conformer of hydrogen and hydrophobic interactions. Further, a 100 ns MD simulation study found the lowest deviation and fluctuations with various intermolecular interactions to stabilise the complexes. Out of 4, the Naloxone molecule showed robust, steady, and stable RMSD 0.23 ± 0.18 nm. Further, MMGBSA analysis supports MD results and found strong binding energy (ΔG) -29.71 ± 4.97 kcal/mol. In Comparative studies with Neu5Ac2en (native substrate) revealed naloxone has a higher affinity for sialidase. The PCA analysis showed that Naloxone and Thalitone were actively located on the active site, and other compounds were flickered. Our extensive computational and statistical report demonstrates that these FDA drugs can be validated as potential sialidase inhibitors.Communicated by Ramaswamy H. Sarma.

Cationic RGD peptidomimetic nanoconjugates as effective tumor targeting gene delivery vectors with antimicrobial potential.

Gene delivery combined with systemic targeting approach has shown promising potential in cancer gene therapy. Peptides are ideal functional motif for constructing biocompatible non-viral gene delivery vehicles. RGD peptides, in particular, are known to recognize the integrin αVß3, which is expressed specifically on angiogenic blood vessels and, therefore, is considered vital for anti-angiogenesis strategies and cancer treatment. In recent times, several RGD peptide-based non-viral gene delivery vectors have been utilized for targeted gene delivery, however, lack in proteolytic stability. In the current study, we have investigated a series of non-naturally modified RGD peptide mimic (MOH) nanoconjugates with low molecular weight branched polyethylenimine (bPEI 1.8 kDa). The projected peptide mimic, Fmoc-FFARKA (MOH), has already been demonstrated to have high binding efficiency for αVß3 integrins and enhanced cell adhesive ability with high stability compared to the natural RGD counterpart. The polymer-peptide, PEI-MOH (PMOH), nanoconjugate vectors have been designed to enhance the tumor targeting ability, therapeutic proficiency, transfection efficiency and proteolytic stability. The synthesized nanoconjugates showed the ability to protect the bound DNA with low cytotoxicity and their pDNA complexes displayed enhanced transfection efficiency. Furthermore, a competitive study confirmed their selective behavior towards liver cancer cells, HepG2. Lastly, PMOH nanoconjugates also exerted significant antimicrobial effects against drug-resistant pathogens. Altogether, the data suggest that nanosized non-naturally modified RGD peptide mimic-based gene vectors hold great potential as efficient biomaterials for targeted gene delivery and antimicrobial applications.

inPhocus: Current State and Challenges of Phage Research in Singapore.

Bacteriophages and phage-derived proteins are a promising class of antibacterial agents that experience a growing worldwide interest. To map ongoing phage research in Singapore and neighboring countries, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore (NTU) and Yong Loo Lin School of Medicine, National University of Singapore (NUS) recently co-organized a virtual symposium on Bacteriophage and Bacteriophage-Derived Technologies, which was attended by more than 80 participants. Topics were discussed relating to phage life cycles, diversity, the roles of phages in biofilms and the human gut microbiome, engineered phage lysins to combat polymicrobial infections in wounds, and the challenges and prospects of clinical phage therapy. This perspective summarizes major points discussed during the symposium and new perceptions that emerged after the panel discussion.

Therapeutic Applications of Self-assembled Indole-3-butanoyl-polyethylenimine Nanostructures.

This study demonstrates the therapeutic potential of indole-3-butanoyl-polyethylenimine (IBP) nanostructures formed via self-assembly in aqueous system. Dynamic light scattering (DLS) analysis confirmed the formation of the nanostructures in the size range of ~ 194-331 nm. These nanostructures showed commendable antimicrobial activity against wide range of microbes including multi-drug resistant bacteria. Besides, appreciable antioxidant and anti-inflammatory activities were also observed. Results of cytotoxicity studies, performed on normal transformed human embryonic kidney (HEK 293) cells and human red blood cells (hRBCs), revealed almost non-toxic behavior of these nanostructures, however, remarkable toxicity on human breast cancer cells (MCF-7), human osteosarcoma cells (Mg63) and human liver cancer cells (HepG2) was observed. The pre-apoptotic and anti-proliferative activity of IBP nanostructures were confirmed by acridine orange/propidium iodide dual staining assay followed by confocal microscopy and scratch assay on Mg63 cells. Taken together, these results advocate the promising potential of the synthesized IBP nanostructures in the therapeutic applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01015-y.

Identification of natural inhibitors to inhibit C. acnes lipase through docking and simulation studies.

Acne vulgaris is a common skin disease affecting 80-90% of teenagers worldwide. C. acnes producing lipases are the main virulence factor that catalyzes sebum lipid into free fatty acid that is used for C. acnes growth. Recently, computational biology and bioinformatics play a significant role in drug discovery programs and the identification of novel lead(s). In this study, potential inhibitors against the C. acnes lipase have been identified via cost-effective computational investigations. Molecular docking, MD simulations, and binding affinity analysis have been performed between the active site of C. acnes lipase protein and selected natural plant constituents. First, C. acnes lipase protein was downloaded from PDB and defined the catalytically active site. Next, 16 active natural plant constituents were shortlisted from the PubChem library (based on their pharmacokinetics, pharmacodynamics, and antibacterial activity). Docking studies identified the best five active compounds that showed significantly strong binding affinity interacted through hydrogen bonding, hydrophobic interactions, and π-stacking with the active site residues of the target protein. Furthermore, a 100 ns MD simulation run showed a stable RMSD and less fluctuating RMSF graph for luteolin and neryl acetate. In silico investigation suggested that luteolin, neryl acetate, and isotretinoin were involved in stable interactions which were maintained throughout the MD run with the C. acnes lipase enzyme, virtually. The results advocated that these could potentially inhibit lipase activity and be used in the clinical management of acne.

Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies.

Given the spasmodic increment in antimicrobial resistance (AMR), world is on the verge of "post-antibiotic era". It is anticipated that current SARS-CoV2 pandemic would worsen the situation in future, mainly due to the lack of new/next generation of antimicrobials. In this context, nanoscale materials with antimicrobial potential have a great promise to treat deadly pathogens. These functional materials are uniquely positioned to effectively interfere with the bacterial systems and augment biofilm penetration. Most importantly, the core substance, surface chemistry, shape, and size of nanomaterials define their efficacy while avoiding the development of AMR. Here, we review the mechanisms of AMR and emerging applications of nanoscale functional materials as an excellent substitute for conventional antibiotics. We discuss the potential, promises, challenges and prospects of nanobiotics to combat AMR.

An injectable self-assembling hydrogel based on RGD peptidomimetic ß-sheets as multifunctional biomaterials.

Ability of the cells to adhere to an extracellular material is central to successful tissue genesis. Arg-Gly-Asp (RGD) sequences found in extracellular matrix proteins are well known for cell adhesion, however, enzymatic degradation and lack of specificity have limited their widespread use. Besides, a multifunctional material with inherent antimicrobial ability would help in invigorating the practical tissue engineering applications. Here, we report novel modified RGD (MR) and RGD mimic [R(K)] peptides (MOH and MNH2) which were synthesized post-in-silico screening, based on their interactions with integrin protein αVß3 using HEX 8.0 docking server. These mimics, containing hydrophobic Phe-Phe (FF) moiety which has been specifically introduced to initiate the self-assembling process of ß-sheet structures, were characterized thoroughly using various physicochemical and spectroscopic techniques. Under physiological conditions, these mimetics displayed thixotropic behavior rendering them highly suitable as injectable hydrogels having an added advantage of site-specific targeting abilities. Electron microscopy further revealed the formation of nanofibers upon self-assembly of these peptides. Besides, enhanced cell adhesiveness by these peptides compared to the commercial Poly l-lysine coated surfaces as well as the inherent antimicrobial potential against both sensitive and antibiotic-resistant pathogens (Methicillin-resistant Staphylococcus aureus and multi-drug resistant Salmonella enteritidis) substantiated the applicability of these unique injectable hydrogels wherein the porous fibrous framework offered a favorable environment for drug entrapment and 3D cell culture. Altogether, these properties render these novel RGD mimic peptides as promising multifunctional candidates for various tissue regenerative applications.

Nano-Therapeutics to Treat Acne Vulgaris.

Nanotechnology is a novel approach to dermatologic treatment. Nanomaterials are materials typically defined as less than 100 nm in size. As this size approaches molecular dimensions, the chemical and physical properties vastly change due to a relative increase in surface area to volume  ratio. Unique and altered properties ensue, such as carbon becoming an electrical conductant in the nano form, and glass becoming a liquid. The interaction of nanoparticles with biota likewise changes. Novel therapeutics may be possible with the use of nanomaterials. Advantages of nanoparticles include the ability to overcome microbial resistance and potentially induce immunomodulatory effects. Engineered nanomaterials or the development of nano-therapeutics with photo-induced antibacterial propensity and immunomodulatory activities has the potential to open new prospects for the treatment of ubiquitous cutaneous diseases, such as acne vulgaris.

Supramolecular self-assemblies of engineered polyethylenimines as multifunctional nanostructures for DNA transportation with excellent antimicrobial activity.

In this study, indole-3-butanoic acid (IBA), a biologically and environmentally safe entity, has been grafted onto low and high molecular weight (1.8 and 25 kDa) polyethylenimines (PEI) mainly through primary amines to obtain amphiphilic indole-3-butanoyl-polyethylenimines (IBPs). Two series of IBPs (IBP1.8 and IBP25) were prepared which, on self-assembly in aqueous medium, yielded multifunctional nanomicellar structures (IBP1.8 and IBP25) capable of transporting genetic material in vitro and exhibiting other biological activities. Physicochemical characterization showed the size of IBP1.8 and IBP25 nanostructures in the range of ~332-234 nm and ~283-166 nm, respectively, with zeta potential varying from ~+29-17 mV and ~+37-25 mV. DNA release assay demonstrated higher release of plasmid DNA from IBP nanostructures as compared to native PEIs. Cytotoxicity showed a decreasing pattern with increasing degree of grafting of IBA onto PEIs making these nanostructures non-toxic. pDNA complexes of these nanostructures (both IBPs1.8 and IBPs25) displayed considerably higher transfection efficiency, however, IBP1.8/pDNA complexes performed much better (~7-9 folds) as compared to native PEI/pDNA and Lipofectamine/pDNA complexes on mammalian cells. CLSM analysis revealed that these complexes entered nucleus in sufficient amounts suggesting higher uptake and efficient internalization of the complexes. Besides, these supramolecular nanostructures not only exhibited excellent antimicrobial potential (MIC ~49-100 µg/ml) against clinical as well as resistant pathogenic strains but also found to possess antioxidant property. Overall, the projected low molecular weight PEI-based vectors could serve as more effective multifunctional nanomaterials having promising potential for future gene therapy applications with capability to provide protection against other bacterial infections.

Biogenic Silver Nanoparticles: Evaluation of Their Biological and Catalytic Potential.

The biogenic tailoring of silver nanoparticles using plant extract is becoming an attractive approach in the current scenario. Manilkara zapota (MZ) is well known for its antibacterial, hepato-protective, anti-inflammatory, anti-tussive, anti-fungal, anti-tumour, and free radical scavenging potential. Its plants extract is a rich source of secondary metabolites. Nowadays, silver nanoparticles (AgNPs) have been advocated for a variety of biomedical applications. In present work, silver nanoparticles have been synthesized using an aqueous extract of MZ, physicochemically characterized and finally evaluated for antimicrobial effects, catalytic reduction/degradation of organic dyes and cytotoxicity. The nanosized AgNPs (~ 84 nm) were found to possess prominent antibacterial potential against gram positive and gram negative pathogens (MIC 50 µg/ml) in comparison to native plant extract. Moreover, these particles were found to be non-toxic and efficient eradicators of environmental toxicants via rapid catalytic reduction of toxic chemicals and dyes. Altogether, these results suggest promising potential of these nanoparticles that can be used as multifunctional agents for future biomedical applications.

Robust dual modality antibacterial action using silver-Prussian blue nanoscale coordination polymer.

We report the synthesis of novel silver-doped Prussian blue nanoscale coordination polymers (SPB NCPs), for dual modality photothermal ablation and oxidative toxicity in bacterial cells. The comparison of SPB NCPs (having Fe-CN-Ag bonds) with the conventionally used Prussian blue nanoscale coordination polymers (PB NCPs, having Fe-CN-Fe bonds) was investigated in terms of their physical and therapeutic properties. It was observed that both PB and SPB NCPs have similar physical dimensions, crystalline phase and optical properties. Both these NCPs showed robust photothermal effect by heat generation (hyperthermia) upon exposure to red laser light. However, among the two, only SPB NCP showed oxidase-like activity by generating H2O2 in aqueous medium, presumably due to its silver content. In vitro antibacterial studies revealed that the SPB NCPs, but not PB NCPs, show inherent toxicity towards bacteria with an IC50 value close to 2.5 µg/ml. It can be inferred that this toxicity is oxidative in nature, as a result of the oxidase-like behaviour shown by SPB NCPs. Furthermore, light activation resulted in substantial additional antibacterial effect (photothermal toxicity) in bacterial cells treated with SPB NCPs. In comparison, marginal additional photothermal toxicity was observed in PB NCP-treated bacteria. Thus, we conclude that the combination of dual modality oxidative and photothermal toxicities demonstrated by SPB NCPs, but not by control PB NCPs, makes the former promising antibacterial agents at low dosages.

Dual Modality FeS Nanoparticles with Reactive Oxygen Species-Induced and Photothermal Toxicity toward Pathogenic Bacteria.

Bacterial infections pose a major threat to human health, primarily because of the evolution of mutated strains that are resistant to antibiotic treatment. As a viable alternative, several nanoparticles have emerged as attractive antibacterial agents. Herein, we report the development of iron sulfide (FeS) nanoparticles that show dual-modality therapy: namely reactive oxygen species (ROS)-induced toxicity and red-laser induced photothermal therapy. The aqueous synthesized nanoparticles have been characterized based on their size, shape, crystallinity, and magnetic and optical properties. These nanoparticles showed sustained release of Fe2+ ions in an aqueous dispersion. They also have a high absorption cross-section in the visible and near infra-red regions and could be excited by a continuous wave diode laser of wavelength 635 nm leading to significant hyperthermia. Nanoparticle treatment, followed by light irradiation, led to significant cell death in two ghastly pathogenic bacterial strains. Stepwise enhancement of intrabacterial ROS levels, as a result of nanoparticle treatment followed by light activation, has been identified as the primary antibacterial mechanism.

Polydopamine -aminoglycoside nanoconjugates: Synthesis, characterization, antimicrobial evaluation and cytocompatibility.

Development of nanoparticle- and self-assembled nanomaterial-based therapeutics has become a rapidly growing area in the field of nanotechnology. One of the natural compounds, dopamine, presents as a neurotransmitter in the human brain serving as a messenger and deals with the behavioural responses, has provided an ideal platform through self-polymerization under aerobic conditions leading to the formation of a beneficial organic biopolymer, polydopamine (PDA). This polymer provides sufficient reactive functionalities, which can further be use to attach amine- or thiol-containing ligands to obtain conjugates. In the present study, self-polymerized polydopamine nanoparticles have been synthesized and tethered to aminoglycosides (AGs: Gentamicin, Kanamycin and Neomycin) through amino moieties to obtain PDA-AG nanoconjugates. These nanoconjugates are characterized by physicochemical techniques and evaluated for their antimicrobial potency against various bacterial strains including resistant ones. Simultaneously, cytocompatibility was also assessed for PDA-AG nanoconjugates. Of these three nanoconjugates (PDA-Gentamicin, PDA-Kanamycin and PDA-Neomycin), PDA-Kanamycin (PDA-K) nanoconjugate exhibited the highest activity against potent pathogens, least toxicity in human embryonic kidney (HEK 293) cells and intense toxic effects on human glioblastoma (U87) cells. Together, these results advocate the promising potential of these nanoconjugates to be used as potent antimicrobials in future applications.