Poornima Dubey

Perturbation of cellular mechanistic system by silver nanoparticle toxicity: Cytotoxic, genotoxic and epigenetic potentials

Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due to the advancement of nanotechnology. However, only limited information is available with regard to their toxicity mechanism in different species. It is very essential to understand the complete molecular mechanism to explore the functional and long term applications of Ag NPs. Ag NPs could be toxic at cellular, subcellular, biomolecular, and epigenetic levels. Toxicity effects induced by Ag NPs have been evaluated using numerous in vitro and in vivo models, but still there are contradictions in interpretations due to disparity in methodology, test endpoints and several other model parameters which needs to be considered. Thus, this review article focuses on the progressive elucidation of molecular mechanism of toxicity induced by Ag NPs in various in vitro and in vivo models. Apart from these, this review also highlights the various ignored factors which are to be considered during toxicity studies.

A novel one-step synthesis of PEG passivated multicolour fluorescent carbon dots for potential biolabeling application

Poly(ethylene glycol) passivated multicolour fluorescent carbon dots (CPs) were synthesised by a novel one-step method and their biolabeling mechanism was studied using S. aureus and recombinant green fluorescent protein (GFP)-expressing E.coli as model systems. The mechanism of formation of fluorescent carbon nanorods from CPs was also explored.

Emerging applications of nanoparticles for lung cancer diagnosis and therapy

Lung cancer is by far the leading cause of cancer-related mortality worldwide, most of them being active tobacco smokers. Non small cell lung cancer accounts for around 85% to 90% of deaths, whereas the rest is contributed by small cell lung cancer. The extreme lethality of lung cancer arises due to lack of suitable diagnostic procedures for early detection of lung cancer and ineffective conventional therapeutic strategies. In course with desperate attempts to address these issues independently, a multifunctional nanotherapeutic or diagnostic system is being sought as a favorable solution. The manifestation of physiochemical properties of such nanoscale systems is tuned favorably to come up with a versatile cancer cell targeted diagnostic and therapeutic system. Apart from this, the aspect of being at nanoscale by itself confers the system with an advantage of passive accumulation at the site of tumor. This review provides a broad perspective of three major subclasses of such nanoscale therapeutic and diagnostic systems which include polymeric nanoparticles-based approaches, metal nanoparticles-based approaches, and bio-nanoparticles-based approaches. This review work also serves the purpose of gaining an insight into the pros and cons of each of these approaches with a prospective improvement in lung cancer therapeutics and diagnostics.

Combined effect of cellulose nanocrystal and reduced graphene oxide into poly-lactic acid matrix nanocomposite as a scaffold and its anti-bacterial activity

In the present study, cellulose nanocrystals (CNCs) and reduced graphene oxide (rGO) were successfully synthesized via acid hydrolysis and modified Hummers method, respectively. Further, the synthesized CNCs and rGO were incorporated into poly-lactic acid (PLA) matrix using solution casting method utilizing different weight (wt.) % of CNCs (nanofiller) and rGO. The successful synthesis of various nanoformulations were confirmed by several characterization techniques including Transmission Electron Microscopy (TEM), Field-Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared Spectroscopy (FTIR) analysis. Hydrophilicity measurement of the film was done by wettability analysis. The mechanical property evaluation of scaffold showed considerable increased tensile strength of PLA/CNC/rGO nanocomposite upto 23%, with increase in elongation at break (εb) indicating the ductile behavior of nanocomposite as compare to pristine PLA. The distinct anti-bacterial efficacy of PLA/CNC/rGO nanocomposite film was found against both Gram positive Staphylococcus aureus (S.aureus) and Gram negative Escherichia coli. (E. coli) bacterial strains respectively. Furthermore the in-vitro cell based cytotoxicity assay showed negligible cytotoxicity of fibroblast cell line (NIH-3T3) upon treatment with nanocomposite film. Therefore, the as fabricated nanocomposite film possesses considerable potential in biomedical as well as in food packaging applications.

Fabrication of electrospun poly(ethylene oxide)–poly(capro lactone) composite nanofibers for co-delivery of niclosamide and silver nanoparticles exhibits enhanced anti-cancer effects in vitro

An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, which hindered their translation from laboratory to clinics. In an effort to enhance their water solubility and bioavailability, we have developed simplistic strategies based on the solvent evaporation and amorphous solid dispersion methods. Among various solvent evaporation methods, electrospinning was adopted in the present work. Poly(ethylene oxide) (PEO) was selected as the polymeric solid dispersion matrix of the drug based on various advantageous properties of PEO. Moreover PEO could also serve as a template for the in situ synthesis of silver nanoparticles (Ag NPs). Furthermore the co-delivery of multiple anticancer drugs within a nanocarrier is a promising approach to overcome the drug resistance and to achieve synergistic therapy. To achieve this goal, the drugs (niclosamide (nic)) and Ag NPs were loaded separately and together (nic@Ag NPs) into the nanofiber. The as-prepared various formulations of composite nanofibers were well-characterized by different techniques. The in vitro release and kinetic studies suggest the sustained release of niclosamide which followed Fickian diffusion kinetics. The anticancer potential of the drugs alone and the nic@Ag NPs loaded nanofibers were evaluated by MTT assay against A549 (lung carcinoma) and MCF-7 (breast carcinoma) cell lines. The co-delivery of anticancer drugs nic@Ag NPs from nanofibers displayed superior anticancer potential in vitro when compared to nic alone or Ag NPs composite nanofibers. Additionally nic@Ag NPs showed better therapeutic efficacy against MCF-7 cells. To confirm the mechanism of cell death by nic@Ag NP composite nanofibers on MCF-7 cells, various cell based assays were done. Our finding clearly explains that a combination of drugs with the diverse anticancer mechanism remarkably improved the therapeutic potential of drugs. Therefore, the nic@Ag NPs composite nanofiber as a co-delivery system might have potential applications in combination cancer therapy.

Bionanotherapeutics: niclosamide encapsulated albumin nanoparticles as a novel drug delivery system for cancer therapy

One of the major unresolved challenges among the scientific community is to develop anticancer drugs that are safe and effective. A large number of anticancer drugs have been screened so far in this campaign. Among them niclosamide has shown tremendous anti-cancer potential as demonstrated in a surfeit of human cancer cell lines and animal models. But the extreme hydrophobicity and consequently, minimal systemic bioavailability associated with this drug limited its widespread clinical applications. Nanoparticles based drug delivery systems have the potential for realizing water soluble formulation of highly hydrophobic anticancer drugs like niclosamide, thus evading the drawbacks of poor solubility. In this work niclosamide was encapsulated into albumin nanoparticles through a desolvation method to improve its scope of application in cancer therapy. Physico-chemical characterization confirms that the prepared nanoparticles are spherical, highly monodispersed, and stable in aqueous systems. These drug encapsulated albumin nanoparticles, unlike the free drug demonstrate better in vitro therapeutic efficacy against human lung and breast cancer cell lines, as assessed by cell viability assay and morphological analyses. Further, the proficient induction of apoptosis by these nanoparticles was confirmed by semi-quantitative RT-PCR. This work open up a new avenue to extend the clinical gamut of this effectual agent by enabling its aqueous dispersion.

PEGylated graphene oxide-based nanocomposite-grafted chitosan/polyvinyl alcohol nanofiber as an advanced antibacterial wound dressing

Designing composite nanomaterials that display multiple antibacterial mechanisms offers new prototype against bacterial resistance. This study presents a multi-component composite-based nanofiber embodying the antibacterial and physiochemical properties of silver nanoparticles (Ag NPs), graphene oxide (GO), chitosan (CS), and curcumin (CUR). Physiologically stable PEGylated GO–Ag NP–CUR nanocomposites were synthesized, with the PEGylated GO serving as the template. The as-synthesized nanocomposite was incorporated into the CS/polyvinyl alcohol (PVA) nanofiber. The successful formation and stability of the PEGylated-GO–Ag NP–CUR composite nanofiber were characterized by various techniques. The antibacterial potential of the PEGylated-GO–Ag NP–CUR composite nanofiber was evaluated and showed an enhanced antibacterial effect compared to various nanoformulations. The plausible antibacterial mechanism of the PEGylated-GO–Ag NP–CUR nanofiber was determined and depicted herein. The presence of GO in the composite nanofiber enhances its mechanical properties compared to CS/PVA nanofiber, with an ultimate tensile strength (UTS) of 25 MPa compared to 7.2 MPa and a Youngs modulus (E) of 363.7 MPa compared to 73 MPa. The biocompatibility of the nanofiber mat was confirmed by in vitro cell viability assay. Therefore a facile approach for the design of a biocompatible wound dressing with enhanced mechanical and antibacterial property was explored and detailed herein.