Application of nanoparticles for management of plant viral pathogen: Current status and future prospects.

Plant viruses are responsible for nearly 47 % of all crop losses brought by plant diseases, which have a considerable negative impact on agricultural output. Nanoparticles have the potential to greatly raise agricultural output due to their wonderful applications in the fields of highly sensitive biomolecular detection, disease diagnostics, antimicrobials, and therapeutic compounds. The application of nanotechnology in plant virology is known as nanophytovirology, and it involves biostimulation, drug transport, genetic manipulation, therapeutic agents, and induction of plant defenses. The inactivation and denaturation of capsid protein, nucleic acids (RNA or DNA), and other protein constituents are involved in the underlying mechanism. To determine the precise mechanism by which nanoparticles affect viral mobility, reproduction, encapsidation, and transmission, more research is however required. Nanoparticles can be used to precisely detect plant viruses using nanobiosensors or as biostimulants. The varieties of nanoparticles employed in plant virus control and their methods of virus suppression are highlighted in this review.

Insights into the challenging multi-country outbreak of Mpox: a comprehensive review.

Human monkeypox virus (hMpoxV) is of zoonotic origin and is closely related to the once-dreaded smallpox virus. It is largely endemic to the African continent but has moved out of the endemic regions as sporadic clusters in the past 20 years, raising concerns worldwide. Human Mpox is characterized by a mild to severe, self-limiting infection, with mortality ranging from less than 1% to up to 10% during different outbreaks caused by different clades of MpoxV. Bushmeat hunting is one of the primary reasons for its transmission from animals to humans. Various international and national health regulatory bodies are closely monitoring the disease and have laid down guidelines to manage and prevent hMpox cases. Emergency Use Status has been granted to Tecovirimat and Brincidofovir to treat severe cases and vaccination with the smallpox vaccine is recommended for high-risk group individuals. Strategies to repurpose and discover novel therapeutics and vaccines to control the outbreak are being researched. The current Mpox outbreak that has mainly affected men as approximately 96% of all cases are reported in men, is probably the result of a complex intersection of various factors. This necessitates a strong One Health response coordination involving human, animal and environmental health institutions. This review is an attempt to provide an all-inclusive overview of the biology, history, epidemiology, pathophysiology, diagnosis and management of hMpox in context to the recent 2022-2023 multi-country outbreak which is termed by WHO a 'Public Health Emergency of International Concern (PHEIC)'.

Anticancer potential of AgNPs synthesized using Acinetobacter sp. and Curcuma aromatica against HeLa cell lines: A comparative study.

BACKGROUND: Biogenic nanoparticles are gaining attention due to their low toxicity and numerous biomedical applications. Present study aimed to compare the potential anticancer activity of two biogenic silver nanoparticles (bAgNPs and pAgNPs) against human cervical cancer cell lines (HeLa). METHODS: bAgNPs were synthesized using Acinetobacter sp. whereas pAgNPs were synthesized using aqueous root extract of Curcuma aromatica. Effect of these nanoparticles on HeLa cells viability was studied using MTT assay and colony formation assay. Anticancer potential was determined using fluorescence microscopy and flow cytometry studies. Bio-compatibility studies were performed against peripheral blood mononuclear cells (PBMCs). RESULTS: Both the nanoparticles showed 50 % viability of peripheral blood mononuclear cells (PBMCs) when used at high concentration (200 µg/mL). IC50 for bAgNPs and pAgNPs against HeLa cells were 17.4 and 14 µg/mL respectively. Colony formation ability of Hela cells was reduced on treatment with both nanoparticles. Acridine orange and ethidium bromide staining demonstrated that bAgNPs were cytostatic whereas pAgNPs were apoptotic. JC-1 dye staining revealed that the mitochondrial membrane potential was affected on treatment with pAgNPs while it remained unchanged on bAgNPs treatment. Flow cytometry confirmed cell cycle arrest in HeLa cells on treatment with nanoparticles further leading to apoptosis in case of pAgNPs. About 77 and 58 % HeLa cells were found in subG1 phase on treatment with bAgNPs and pAgNPs respectively. bAgNPs showed cytostatic effect on HeLa cells arresting the cell growth in subG1 phase, whereas, pAgNPs triggered death of HeLa cells through mitochondrial membrane potential impairment and apoptosis. CONCLUSION: Overall, bAgNPs and pAgNPs could be safe and showed potential to be used as anticancer nano-antibiotics against human cervical cancer cells.

Green Synthesis of AuNPs by Acinetobacter sp. GWRVA25: Optimization, Characterization, and Its Antioxidant Activity.

Bacteriogenic synthesis of metal nanoparticles is ecofriendly and greatly influenced by physico-chemical reaction parameters with respect to shape and size. Thus, present work aimed to synthesize and optimization of bacteriogenic gold nanoparticles (AuNPs) and study their antioxidant activity. Acinetobacter sp. cells were able to synthesize AuNPs, when challenged with tetra-chloroauric acid (HAuCl4). By physicochemical optimization, maximum synthesis was obtained with 72 h old culture using 2.1 × 109 CFU/ml cell density. Whereas, pH-7 is suitable for AuNPs synthesis. HAuCl4 concentration (0.5 mM) enhanced the formation of monodispersed and spherical nanoparticles (15 ± 10 nm). At 37°C temperature, Acinetobacter sp. released nanoparticles in supernatant. From characterization, AuNPs were found to be crystalline in nature with negative surface charge. AuNPs showed up to 86% different radical scavenging ability, exhibiting antioxidant activity. In conclusion, spherical AuNPs can be synthesized using Acinetobacter sp. through physicochemical optimization. This is the first report of antioxidant activity exhibited by monodispersed bacteriogenic AuNPs synthesized using Acinetobacter sp.

Purification and Characterization of an Active Principle, Lawsone, Responsible for the Plasmid Curing Activity of Plumbago zeylanica Root Extracts.

Plasmid curing is the process of obviating the plasmid encoded functions such as antibiotic resistance, virulence, degradation of aromatic compounds, etc. in bacteria. Several plasmid curing agents have been reported in literature, however, no plasmid curing agent can eliminate all plasmids from different hosts. Hence, there is always a need for novel plasmid curing agents that can be effectively used for reversal of plasmid encoded functions such as virulence, antibiotic resistance, etc. In the present study, an active principle responsible for the plasmid curing activity was purified from roots of Plumbago zeylanica by bioassay guided fractionation and identified as 2-hydroxy-1,4-naphthoquinone (lawsone), on the basis of spectral and analytical data such as NMR, GCMS, FTIR. Plasmid curing activity of lawsone was observed against reference as well as wild plasmids (pBR322, pRK2013, R136, pUPI281, and pUPI282) residing in a range of hosts. Curing of plasmid was confirmed by agarose gel electrophoresis. MICs of antibiotics against A. baumannii A24 (pUPI281) and E. coli (pRK2013) decreased significantly in presence of lawsone suggesting synergy between lawsone and antibiotics. Lawsone also inhibited transfer of plasmid pRK2013 to E. coli either by transformation or conjugation. Viability assays (MTT) revealed that lawsone was not toxic to mammalian cells. Thus, the present investigation has revealed lawsone as an effective plasmid curing agent capable of suppressing development and spread of antibiotic resistance. Further, lawsone has important application in basic research to identify phenotypes encoded by the plasmids in plasmid curing experiments. To the best of our knowledge this is the first report of plasmid curing activity of lawsone isolated from roots of P. zeylanica.

Antibacterial Activities of Bacteriagenic Silver Nanoparticles Against Nosocomial Acinetobacter baumannii.

Acinetobacter baumannii has emerged as one of the major nosocomial pathogens implicated in variety of severe infections and mortality. It is rapidly developing multi-drug resistance and also possesses surface colonization ability, which make it most difficult to treat through traditional antibiotics. This is an extensive study to describe the antibacterial activity of bacteriagenic silver nanoparticles (AgNPs) against A. baumannii AIIMS 7 in planktonic and biofilm mode. Minimum inhibitory concentration of antibiotics were in the range of 1 to 4096 µg/ml whereas AgNPs inhibited planktonic bacteria at concentration of 16 µg/ml. Fractional inhibitory concentration index revealed the synergistic interaction of AgNPs with doxycycline, tetracycline and erythromycin. Nanoparticles exhibited significant biofilm disruption activity with minimum biofilm eradication concentration of 2 mg/ml. Eradication of mature biofilm was enhanced on exposure to combination of AgNPs and antibiotics. These nanoparticles affected bacterial growth and distorted cellular morphology. Intracellular oxidative stress, induced in presence of AgNPs, also rendered bacteria susceptible to killing by nanoparticles. Besides this, AgNPs were found to interact with thiol-groups, which indicate their potential to interact with cellular proteins to exhibit antimicrobial activity.

Biosynthesis of gold and selenium nanoparticles by purified protein from Acinetobacter sp. SW 30.

Synthesis of nanoparticles is an enzymatic reduction process in microorganisms. In the present study, a protein, lignin peroxidase has been purified by DEAE-Cellulose anion exchange chromatography and Biogel P-150 gel filtration chromatography from the cell suspension of Acinetobacter sp. SW30 responsible for the synthesis of gold nanoparticles (AuNP) and selenium nanoparticles (SeNP). The purified fraction has a specific activity of 29.4U/mg/min with 959 fold purification. Native and SDS PAGE confirmed that purified lignin peroxidase is monomeric enzyme with 97.4KDa molecular weight. The enzyme synthesized spherical crystalline AuNP (10±2nm) and amorphous SeNP (100±10nm). It has maximum activity at pH 2 and temperature 40°C, with 1.0mMKm value, when n-propanol was used as a substrate. Activity was completely inhibited by sodium thiosulphate and zinc sulphate. This is the first report on association of lignin peroxidase in the synthesis of AuNP and SeNP from Acinetobacter sp. SW30.

Lignin peroxidase mediated silver nanoparticle synthesis in Acinetobacter sp.

Metals present in environment render the bacteria to attain certain resistance machinery to survive, one of which is transformation of metal ions to nano forms. Various enzymes and proteins have been suggested to play significant role in synthesis of silver nanoparticles (AgNPs) in bacteria. In present study, we have purified lignin peroxidase from secreted enzyme extract of Acinetobacter sp. employing diethyl aminoethyl cellulose ion exchange and Biogel P-150 gel filtration column chromatography. The purified fraction has a specific activity of 1.571 U/mg with substrate n-propanol and 6.5-fold purification. The tetrameric enzyme, with molecular weight of 99 kDa, consisted of dimers of two polypetides of 23.9 and 24.6 kDa as revealed by native and SDS-PAGE. On exposure to purified enzyme, spherical polydispersed AgNPs of ~ 50 nm were obtained as observed under transmission electron microscope. Optimum activity of the purified enzyme was obtained at pH 2 and 60 °C with n-propanol as substrate. This is the first report describing the reduction of extracellular silver ions by lignin peroxidase purified from Acinetobacter sp.

Green synthesis of selenium nanoparticles using Acinetobacter sp. SW30: optimization, characterization and its anticancer activity in breast cancer cells.

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×109 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na2SeO3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents.

Kinetics of Synthesis of Gold Nanoparticles by Acinetobacter sp. SW30 Isolated from Environment.

Cell biomass and metal salt concentration have great influence on morphology of biosynthesized nanoparticle. The aim of present study was to evaluate the effect of varying cell density and gold salt concentrations on synthesis of nanoparticles and its morphology, which has not been studied in bacteria till now. When cells of Acinetobacter sp. SW30 were incubated with different cell density and gold chloride concentrations, tremendous variation in color of colloidal solution containing gold nanoparticles (AuNP) was observed indicating variation in their size and shapes. Surprisingly, monodispersed spherical AuNP of size ~19 nm were observed at lowest cell density and HAuCl4 salt concentration while increase in cell number resulted in formation of polyhedral AuNP (~39 nm). Significance of this study lays in the fact that the shape and dispersity of AuNP can be customized depending up on the requirement. FTIR spectrum revealed shift from 3221 to 3196 cm-1 indicating the presence and role of amino acids in Au3+ reduction while possible involvement of amide I and II groups in stabilization of AuNP. The rate constant was calculated for cell suspension of 2.1 × 109 cfu/ml challenged with 1.0 mM HAuCl4, incubated at 30 °C and pH 7 using the slopes of initial part of the plot log (Aα - At) versus time as 1.99 × 10-8 M. Also, this is the first study to report the kinetics of gold nanoparticle synthesis by Acinetobacter sp. SW30.

Phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents.

PURPOSE: Multi- and extensively drug-resistant tuberculosis (TB) is a global threat to human health. It requires immediate action to seek new antitubercular compounds and devise alternate strategies. Nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. In view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria. METHODS: Silver (AgNPs), gold (AuNPs), and gold-silver bimetallic (Au-AgNPs) nanoparticles synthesized from medicinal plants, such as Barleria prionitis, Plumbago zeylanica, and Syzygium cumini, were tested against Mycobacterium tuberculosis and M. bovis BCG. In vitro and ex vivo macrophage infection model assays were designed to determine minimum inhibitory concentration (MIC) and half maximal inhibitory concentration of nanoparticles. Microscopic analyses were carried out to demonstrate intracellular uptake of nanoparticles in macrophages. Besides this, biocompatibility, specificity, and selectivity of nanoparticles were also established with respect to human cell lines. RESULTS: Au-AgNPs exhibited highest antitubercular activity, with MIC of <2.56 µg/mL, followed by AgNPs. AuNPs did not show such activity at concentrations of up to 100 µg/mL. In vitro and ex vivo macrophage infection model assays revealed the inhibition of both active and dormant stage mycobacteria on exposure to Au-AgNPs. These nanoparticles were capable of entering macrophage cells and exhibited up to 45% cytotoxicity at 30 µg/mL (ten times MIC concentration) after 48 hours. Among these, Au-AgNPs synthesized from S. cumini were found to be more specific toward mycobacteria, with their selectivity index in the range of 94-108. CONCLUSION: This is the first study to report the antimycobacterial activity of AuNPs, AgNPs, and Au-AgNPs synthesized from medicinal plants. Among these, Au-AgNPs from S. cumini showed profound efficiency, specificity, and selectivity to kill mycobacteria. These should be investigated further to develop novel TB nanoantibiotics.

Biogenic selenium nanoparticles: current status and future prospects.

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicine owing to their antibacterial and anticancer properties. SeNPs are biocompatible and non-toxic compared to the counterparts, selenite (SeO3 (-2)) and selenate (SeO4 (-2)). They can be synthesized by physical, chemical, and biological methods and have distinct bright orange-red color. Biogenic SeNPs are stable and do not aggregate owing to natural coating of the biomolecules. Various hypotheses have been proposed to describe the mechanism of microbial synthesis of SeNPs. It is primarily a two-step reduction process from SeO4 (-2) to SeO3 (-2) to insoluble elemental selenium (Se(0)) catalyzed by selenate and selenite reductases. Phenazine-1-carboxylic acid and glutathione are involved in selenite reduction. Se factor A (SefA) and metalloid reductase Rar A present on the surface of SeNPs confer stability to the nanoparticles. SeNPs act as potent chemopreventive and chemotherapeutic agents. Conjugation with antibiotics enhances their anticancer efficacy. These also have applications in nanobiosensors and environmental remediation.

Nanoparticles for Control of Biofilms of Acinetobacter Species.

Biofilms are the cause of 80% of microbial infections. Acinetobacter species have emerged as multi- and pan-drug-resistant bacteria and pose a great threat to human health. These act as nosocomial pathogens and form excellent biofilms, both on biotic and abiotic surfaces, leading to severe infections and diseases. Various methods have been developed for treatment and control of Acinetobacter biofilm including photodynamic therapy, radioimmunotherapy, prophylactic vaccines and antimicrobial peptides. Nanotechnology, in the present scenario, offers a promising alternative. Nanomaterials possess unique properties, and multiple bactericidal mechanisms render them more effective than conventional drugs. This review intends to provide an overview of Acinetobacter biofilm and the significant role of various nanoparticles as anti-biofouling agents, surface-coating materials and drug-delivery vehicles for biofilm control and treatment of Acinetobacter infections.

Diosgenin Functionalized Iron Oxide Nanoparticles as Novel Nanomaterial Against Breast Cancer.

Iron oxide nanoparticles (IONPs) have gained immense importance recently as drug nanocarriers due to easy multifunctionalization, simultaneous targeting, imaging and cancer hyperthermia. Herein, we report a novel nanomedicine comprising of IONPs core functionalized with a potent anticancer bioactive principle, diosgenin from medicinal plant Dioscorea bulbifera via citric acid linker molecule. IONPs were synthesized by reverse co-precipitation and characterized using field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). Diosgenin functionalization was confirmed using fourier transform infrared spectroscopy (FTIR) and biochemical methods. Synthesized IONPs, citrate linked IONPs (IONPs-CA), diosgenin functionalized IONPs (IONPs-D) along with free citric acid and diosgenin were checked for anticancer activity against MCF7 breast cancer cells by MTT assay, wound migration assay, confocal microscopy and protein expression by western blotting. Size of IONPs, IONPs-CA and IONPs-D gradually increased ranging from 12 to 21 nm as confirmed by FESEM and HRTEM. Signature peaks of diosgenin at 2914, 1166 and 1444 cm-1 IONPs-D, revealed in FTIR indicated the presence of functionalized diosgenin. IONPs-D exhibited 51.08 ± 0.37% antiproliferative activity against MCF7 cells, which was found to be superior to free citric acid (17.71 ± 0.58%) and diosgenin (33.31 ± 0.37%). Treatment with IONPs-D exhibited reduced wound migration upto 40.83 ± 2.91% compared to bare IONPs (89.03 ± 2.58%) and IONPs-CA (50.35 ± 0.48%). IONPs-D and diosgenin exhibited apoptosis induction, confirmed by Alexa Fluor 488 annexin V/PI double-stained cells indicating extensive cell membrane damage coupled with PI influx leading to nuclear staining in treated cells. IONPs-D mediated selective PARP cleavage strongly rationalized it as superior apoptotic inducers. Based on these findings, IONPs-D can be considered as first diosgenin functionalized novel magnetic nanomedicine with antiproliferative, migration inhibiting and apoptosis inducing properties against breast cancer.

Curcumin-Loaded, Self-Assembled Aloevera Template for Superior Antioxidant Activity and Trans-Membrane Drug Release.

Fine combination of natural botanical extracts to evaluate and maximize their medicinal efficacy has been studied for long. However, their limited shelf-life, complicated extraction protocols, and difficult compositional analysis have always been a problem. It is due to this that such materials take time to convert them into a proper pharmaceutical technology or product. In this context, we report on synthesis of self-assembled template of one of the most popular natural product, aloevera. This forms a fine porous membrane like structure, in which a natural drug, curcumin has been immobilized/trapped. The so-made curcumin-loaded-aloevera (CLA) structures have been carefully evaluated using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-vis spectroscopy and fluorescence microscopy. While FTIR shows that there is no chemical interaction between aloevera and curcumin, the pores are finely occupied by curcumin molecules. Fine microscopy structures reveal their distribution and fluorescence microscopy confirm the presence of curcumin within the pores. TGA shows 15% loading of the curcumin in the template and UV-visible spectroscopy data shows independent peaks of both, aloevera (196 nm and 256 nm) and curcumin (423 nm), respectively. When subjected to antioxidant studies, using DPPH assays, CLAs show a synergistically superior DPPH radical scavenging activity as compared to only curcumin and only aloevera extract. Same is true for hydroxyl and NO2 radicals. Trans-membrane release study reveals that there is no significant difference in the amount of curcumin release from CLAs till initial 30 min, however, it increases steadily thereafter. CLA is found to facilitate efficient release of curcumin in 5 h, which is higher as compared to the curcumin alone.

ZnO Nanoparticles-Red Sandalwood Conjugate: A Promising Anti-Diabetic Agent.

With the advances in nanoscience and nanotechnology the interest of researchers has expanded to interdisciplinary domain like bio-medical applications. Among such domains, one of the most important areas explored meticulously is the development of promising solutions in diabetes therapeutics. The disease associated with metabolic disorder, is one of the major challenges, due to its ever-increasing number of patients. The adverse effects of the synthetic enzymes like α-amylase and α-glucosidase inhibitors have invited many scientists to develop promising contender with minimal side-effects. On the other hand, Zinc has strong role in insulin synthesis, storage and secretion and thus its deficiency can be related to diabetes. In this context we have explored natural extract of Red Sandalwood (RSW) as a potent anti-diabetic agent, in conjugation with ZnO nanoparticles. ZnO nanoparticles have been synthesized via soft chemistry routes and duly characterized for their phase formation with the help of X-ray diffraction technique and Field-Emission Scanning Electron Microscopy. These monodispersed nanoparticles, -20 nm in size, were further conjugated to RSW extract. The conjugation chemistry was studied via Fourier transform infrared spectroscopy, UV-visible spectroscopy. Extract loading percentage was found from thermo-gravimetric analysis. 65% of the RSW extract was found conjugated to the ZnO nanoparticles. The anti-diabetic activity was assessed with the help of like α-amylase and α-glucosidase inhibition assay with murine pancreatic and small intestinal extracts. It was observed that the conjugated ZnO-RSW nanoparticles showed excellent activity against the crude murine pancreatic glucosidase as compared to the individual ZnO nanoparticles and the RSW extract. The ZnO-RSW conjugate showed 61.93% of inhibition while the bare ZnO nanoparticles and RSW showed 21.48% and 5.90% respectively.

Molecular characterization of outer membrane vesicles released from Acinetobacter radioresistens and their potential roles in pathogenesis.

Acinetobacter radioresistens is an important member of genus Acinetobacter from a clinical point of view. In the present study, we report that a clinical isolate of A. radioresistens releases outer membrane vesicles (OMVs) under in vitro growth conditions. OMVs were released in distinctive size ranges with diameters from 10 to 150 nm as measured by the dynamic light scattering (DLS) technique. Additionally, proteins associated with or present into OMVs were identified using LC-ESI-MS/MS. A total of 71 proteins derived from cytosolic, cell membrane, periplasmic space, outer membrane (OM), extracellular and undetermined locations were found in OMVs. The initial characterization of the OMV proteome revealed a correlation of some proteins to biofilm, quorum sensing, oxidative stress tolerance, and cytotoxicity functions. Thus, the OMVs of A. radioresistens are suggested to play a role in biofilm augmentation and virulence possibly by inducing apoptosis.

Bacteriagenic silver nanoparticles: synthesis, mechanism, and applications.

Silver nanoparticles (AgNPs) have received tremendous attention due to their significant antimicrobial properties. Large numbers of reports are available on the physical, chemical, and biological syntheses of colloidal AgNPs. Since there is a great need to develop ecofriendly and sustainable methods, biological systems like bacteria, fungi, and plants are being employed to synthesize these nanoparticles. The present review focuses specifically on bacteria-mediated synthesis of AgNPs, its mechanism, and applications. Bacterial synthesis of extra- and intracellular AgNPs has been reported using biomass, supernatant, cell-free extract, and derived components. The extracellular mode of synthesis is preferred over the intracellular mode owing to easy recovery of nanoparticles. Silver-resistant genes, c-type cytochromes, peptides, cellular enzymes like nitrate reductase, and reducing cofactors play significant roles in AgNP synthesis in bacteria. Organic materials released by bacteria act as natural capping and stabilizing agents for AgNPs, thereby preventing their aggregation and providing stability for a longer time. Regulation over reaction conditions has been suggested to control the morphology, dispersion, and yield of nanoparticles. Bacterial AgNPs have anticancer and antioxidant properties. Moreover, the antimicrobial activity of AgNPs in combination with antibiotics signifies their importance in combating the multidrug-resistant pathogenic microorganisms. Multiple microbicidal mechanisms exhibited by AgNPs, depending upon their size and shape, make them very promising as novel nanoantibiotics.

Chemical and biological metal nanoparticles as antimycobacterial agents: A comparative study.

Resistance among mycobacteria leading to multidrug-resistant and extensively drug-resistant tuberculosis is a major threat. However, nanotechnology has provided new insights in drug delivery and medicine development. This is the first comparative report to determine the activity of chemically and biologically synthesised silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mycobacteria. Screening data revealed the high mycobactericidal efficiency of AgNPs, with minimum inhibitory concentrations (MICs) of <3µg/mL, whereas no such activity was exhibited by AuNPs at concentrations up to 100µg/mL. Moreover, in vitro and ex vivo THP-1 infection model assays showed greater efficacy of chemical AgNPs compared with biogenic AgNPs to inhibit active and dormant stage mycobacterial growth. Up to 40% cytotoxicity against human cell lines was observed at a AgNP concentration of 10× MIC (30µg/mL) after 48h. AgNPs were shown to have more specificity towards mycobacteria than towards other Gram-negative and Gram-positive pathogenic bacteria. The selectivity index was found to be in the range of 11-23, indicating the potential of these nanoparticles for use in developing new therapeutics for tuberculosis.

Dual drug conjugated nanoparticle for simultaneous targeting of mitochondria and nucleus in cancer cells.

Effective targeting of mitochondria has emerged as an alternative strategy in cancer chemotherapy. However, considering mitochondria's crucial role in cellular energetics, metabolism and signaling, targeting mitochondria with small molecules would lead to severe side effects in cancer patients. Moreover, mitochondrial functions are highly dependent on other cellular organelles like nucleus. Hence, simultaneous targeting of mitochondria and nucleus could lead to more effective anticancer strategy. To achieve this goal, we have developed sub 200 nm particles from dual drug conjugates derived from direct tethering of mitochondria damaging drug (α- tocopheryl succinate) and nucleus damaging drugs (cisplatin, doxorubicin and paclitaxel). These dual drug conjugated nanoparticles were internalized into the acidic lysosomal compartments of the HeLa cervical cancer cells through endocytosis and induced apoptosis through cell cycle arrest. These nanoparticles damaged mitochondrial morphology and triggered the release of cytochrome c. Furthermore, these nanoparticles target nucleus to induce DNA damage, fragment the nuclear morphology and damage the cytoskeletal protein tubulin. Therefore, these dual drug conjugated nanoparticles can be successfully used as a platform technology for simultaneous targeting of multiple subcellular organelles in cancer cells to improve the therapeutic efficacy of the free drugs.