Poornima Dubey | University College London (original) (raw)

Papers by Poornima Dubey

Critical Reviews™ in Oncogenesis

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Cancer Research

Head and neck cancer kills over 400,000 people each year with the majority of cases being head an... more Head and neck cancer kills over 400,000 people each year with the majority of cases being head and neck squamous cell carcinoma (HNSCC). Despite major advances in cancer treatment, radiation resistance contributes to increased morbidity and mortality of patients with HNSCC. Few FDA-approved radiosensitizers exist for the treatment of HNSCC and the majority are associated with severe adverse effects. Therefore, there is a clear need to examine novel treatment combinations to improve radiosensitivity and HNSCC outcomes. Isothiocyanates enhance response to cytokines, chemotherapy, and radiation in other in vitro and in vivo cancer models, including pancreatic and breast cancer. Isothiocyanates are antioxidants found in cruciferous vegetables such as watercress and broccoli. Phenethyl isothiocyanate (PEITC) was well tolerated by patients in chemopreventative clinical trials and was thus selected for this study. We hypothesize that PEITC radiosensitizes HNSCC cells through increasing DNA...

As a fascinating alternative to overcome the undesired side effects and to improve therapeutic ef... more As a fascinating alternative to overcome the undesired side effects and to improve therapeutic efficacy and water solubility of chemotherapeutic agent tamoxifen (TAM), the simplistic method based on folic acid (FA) tagged amphiphilic graphene oxide (GO) for cell specific delivery was adopted. Besides, FA-GO also served as template for synthesis of Ag NP. Hence, the present study demonstrates a co-delivery system for folate receptor (FR) targeted delivery of anticancer agents TAM and Ag NP for combination therapeutics of breast cancer in vitro. The method involved the syntheses of sulfonate modified GO with FA functionalization which was validated by FTIR and UV-vis analysis. TAM was loaded onto the FA-GO nanocarrier by physi-osorption of hydrophobic drug onto surface with encapsula-tion efficiency (EE) around 98 %. The synthesized FA-GO@AgNP@TAMnanocarrier was physiologically stable with average zeta potential and hydrodynamic size ofÀ40 mV, 167 nm contrarily to alone GO withÀ29.5 mV, 5 nm respectively. Cellular uptake studies revealed specificity of nano-carrier towards FR (+ ve) breast carcinoma (MCF-7 cell line) compared to FR (-ve) lung carcinoma (A549 cell line). Based on cell specificity of nanocarrier, the cytotoxicity of various nano-carrier combinations was investigated towards MCF-7 cells. The combination exhibited superior cytotoxic effect than TAM, Ag NP alone at relatively lower concentrations with notable cell cycle growth arrest in sub-G 1 phase. The FA-GO@AgNP@TAMna-nocarrier showed elevated intracellular reactive oxygen species (ROS) generation with considerable dissipation of mitochon-drial membrane potential (MMP). Furthermore the semi-quantitative RT-PCR analysis showed increased pro-apoptotic genes expression with highest expression of caspase-3. Altogether the study suggests mitochondria mediated apoptotic signaling pathway. These findings suggest the above designed nano-carrier could serve as the potential candidate for targeted combination breast cancer therapy.

: a) Schematic of oncogene silencing mechanism in cancer cell assisted by AKT-siRNA, b) Various n... more : a) Schematic of oncogene silencing mechanism in cancer cell assisted by AKT-siRNA, b) Various nanocarriers as vehicle for AKT-siRNA delivery.

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

An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, wh... more 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.

Journal of Applied Polymer Science, 2015

The aim of this study was to develop stable and porous poly(ethylene oxide) (PEO)-polycaprolacton... more The aim of this study was to develop stable and porous poly(ethylene oxide) (PEO)-polycaprolactone blended and silver nanoparticle (Ag NP) incorporated composite nanofiber scaffolds as antibacterial wound dressings. A facile approach for the in situ synthesis of Ag NPs was explored. In this synthesis method, N,N-dimethylformamide (DMF) was used as a solvent; it also acted as reducing agent for Ag NP formation. The stabilization of Ag NPs in the fibers was accomplished by PEO, which in turn acted as a reducing agent along with DMF. The successful synthesis of crystalline Ag NPs was confirmed by various characterization techniques. Thermogravimetric analysis, wettability, and surface roughness analysis of the nanofibers were done to examine the suitability of the scaffold for wound dressing. The as-synthesized composite nanofibers possessed good roughness, wettability, and antibacterial potential against recombinant green fluorescent proteins expressing antibiotic-resistant Escherichia coli. Thus, the nanofiber scaffold fabricated by this approach could serve as an ideal wound dressing.

RSC Adv., 2015

ABSTRACT One of the major unresolved challenges among the scientific community is to develop anti... more ABSTRACT 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 semiquantitative RT-PCR. This work open up a new avenue to extend the clinical gamut of this effectual agent by enabling its aqueous dispersion.

International Nano Letters, 2013

ABSTRACT Lung cancer is by far the leading cause of cancer-related mortality worldwide, most of t... more ABSTRACT 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.

Advances in Colloid and Interface Science, 2015

Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due... more 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.

Journal of Biomedical Nanotechnology, 2014

Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in... more Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in living organism and thereby protects the cell from oxidative damage. The ferritin protein cages have been used as a reaction vessel for the synthesis of various non-native metallic nanoparticles inside its core and also used as a nanocarrier for various applications. Lack of suitable non-viral carrier for targeted delivery of anticancer drugs and imaging agents is the major problem in cancer therapy and diagnosis. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Recent studies, further establishes ferritin as a multifunctional nanocarrier for targeted cancer diagnosis and therapy. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. This review mainly focuses on the application of ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it also highlights various biomedical applications of ferritin nanocages.

SpringerBriefs in Applied Sciences and Technology, 2015

Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently a... more Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.

Critical Reviews™ in Oncogenesis

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Cancer Research

Head and neck cancer kills over 400,000 people each year with the majority of cases being head an... more Head and neck cancer kills over 400,000 people each year with the majority of cases being head and neck squamous cell carcinoma (HNSCC). Despite major advances in cancer treatment, radiation resistance contributes to increased morbidity and mortality of patients with HNSCC. Few FDA-approved radiosensitizers exist for the treatment of HNSCC and the majority are associated with severe adverse effects. Therefore, there is a clear need to examine novel treatment combinations to improve radiosensitivity and HNSCC outcomes. Isothiocyanates enhance response to cytokines, chemotherapy, and radiation in other in vitro and in vivo cancer models, including pancreatic and breast cancer. Isothiocyanates are antioxidants found in cruciferous vegetables such as watercress and broccoli. Phenethyl isothiocyanate (PEITC) was well tolerated by patients in chemopreventative clinical trials and was thus selected for this study. We hypothesize that PEITC radiosensitizes HNSCC cells through increasing DNA...

As a fascinating alternative to overcome the undesired side effects and to improve therapeutic ef... more As a fascinating alternative to overcome the undesired side effects and to improve therapeutic efficacy and water solubility of chemotherapeutic agent tamoxifen (TAM), the simplistic method based on folic acid (FA) tagged amphiphilic graphene oxide (GO) for cell specific delivery was adopted. Besides, FA-GO also served as template for synthesis of Ag NP. Hence, the present study demonstrates a co-delivery system for folate receptor (FR) targeted delivery of anticancer agents TAM and Ag NP for combination therapeutics of breast cancer in vitro. The method involved the syntheses of sulfonate modified GO with FA functionalization which was validated by FTIR and UV-vis analysis. TAM was loaded onto the FA-GO nanocarrier by physi-osorption of hydrophobic drug onto surface with encapsula-tion efficiency (EE) around 98 %. The synthesized FA-GO@AgNP@TAMnanocarrier was physiologically stable with average zeta potential and hydrodynamic size ofÀ40 mV, 167 nm contrarily to alone GO withÀ29.5 mV, 5 nm respectively. Cellular uptake studies revealed specificity of nano-carrier towards FR (+ ve) breast carcinoma (MCF-7 cell line) compared to FR (-ve) lung carcinoma (A549 cell line). Based on cell specificity of nanocarrier, the cytotoxicity of various nano-carrier combinations was investigated towards MCF-7 cells. The combination exhibited superior cytotoxic effect than TAM, Ag NP alone at relatively lower concentrations with notable cell cycle growth arrest in sub-G 1 phase. The FA-GO@AgNP@TAMna-nocarrier showed elevated intracellular reactive oxygen species (ROS) generation with considerable dissipation of mitochon-drial membrane potential (MMP). Furthermore the semi-quantitative RT-PCR analysis showed increased pro-apoptotic genes expression with highest expression of caspase-3. Altogether the study suggests mitochondria mediated apoptotic signaling pathway. These findings suggest the above designed nano-carrier could serve as the potential candidate for targeted combination breast cancer therapy.

: a) Schematic of oncogene silencing mechanism in cancer cell assisted by AKT-siRNA, b) Various n... more : a) Schematic of oncogene silencing mechanism in cancer cell assisted by AKT-siRNA, b) Various nanocarriers as vehicle for AKT-siRNA delivery.

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

An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, wh... more 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.

Journal of Applied Polymer Science, 2015

The aim of this study was to develop stable and porous poly(ethylene oxide) (PEO)-polycaprolacton... more The aim of this study was to develop stable and porous poly(ethylene oxide) (PEO)-polycaprolactone blended and silver nanoparticle (Ag NP) incorporated composite nanofiber scaffolds as antibacterial wound dressings. A facile approach for the in situ synthesis of Ag NPs was explored. In this synthesis method, N,N-dimethylformamide (DMF) was used as a solvent; it also acted as reducing agent for Ag NP formation. The stabilization of Ag NPs in the fibers was accomplished by PEO, which in turn acted as a reducing agent along with DMF. The successful synthesis of crystalline Ag NPs was confirmed by various characterization techniques. Thermogravimetric analysis, wettability, and surface roughness analysis of the nanofibers were done to examine the suitability of the scaffold for wound dressing. The as-synthesized composite nanofibers possessed good roughness, wettability, and antibacterial potential against recombinant green fluorescent proteins expressing antibiotic-resistant Escherichia coli. Thus, the nanofiber scaffold fabricated by this approach could serve as an ideal wound dressing.

RSC Adv., 2015

ABSTRACT One of the major unresolved challenges among the scientific community is to develop anti... more ABSTRACT 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 semiquantitative RT-PCR. This work open up a new avenue to extend the clinical gamut of this effectual agent by enabling its aqueous dispersion.

International Nano Letters, 2013

ABSTRACT Lung cancer is by far the leading cause of cancer-related mortality worldwide, most of t... more ABSTRACT 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.

Advances in Colloid and Interface Science, 2015

Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due... more 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.

Journal of Biomedical Nanotechnology, 2014

Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in... more Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in living organism and thereby protects the cell from oxidative damage. The ferritin protein cages have been used as a reaction vessel for the synthesis of various non-native metallic nanoparticles inside its core and also used as a nanocarrier for various applications. Lack of suitable non-viral carrier for targeted delivery of anticancer drugs and imaging agents is the major problem in cancer therapy and diagnosis. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Recent studies, further establishes ferritin as a multifunctional nanocarrier for targeted cancer diagnosis and therapy. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. This review mainly focuses on the application of ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it also highlights various biomedical applications of ferritin nanocages.

SpringerBriefs in Applied Sciences and Technology, 2015

Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently a... more Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.