Vilwanathan Ravikumar

Origanum vulgare mediated biosynthesis of silver nanoparticles for its antibacterial and anticancer activity

In the present study, we achieved silver nanoparticles using the aqueous extract of Origanum vulgare (Oregano) by reducing 1mM silver nitrate (AgNO3) solution. The green synthesized silver nanoparticles were characterized by high throughput techniques like UV-vis spectroscopy, Fourier infrared spectroscopy (FT-IR), field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD) and dynamic light scattering measurements. Morphologically, the nanoparticles were found to be spherical with an average particle size distribution of 136±10.09nm. FT-IR spectral analysis illustrates the occurrence of possible biomolecules required for the reduction of silver ions. The obtained nanoparticles were stable (-26±0.77mV) at ambient temperature. The biosynthesized nanoparticles were found to be impressive in inhibiting human pathogens. The green synthesized silver nanoparticles showed dose dependent response against human lung cancer A549 cell line (LD50 - 100μg/ml).

Green synthesis of colloidal copper oxide nanoparticles using Carica papaya and its application in photocatalytic dye degradation.

Copper oxide (CuO) nanoparticles were synthesized by treating 5 mM cupric sulphate with Carica papaya leaves extract. The kinetics of the reaction was studied using UV-visible spectrophotometry. An intense surface Plasmon resonance between 250-300 nm in the UV-vis spectrum clearly reveals the formation of copper oxide nanoparticles. The results of scanning electron microscopy (SEM) and dynamic light scattering (DLS) exhibited that the green synthesized copper oxide nanoparticles are rod in shape and having a mean particle size of 140 nm, further negative zeta potential disclose its stability at -28.9 mV. The Fourier-transform infrared (FTIR) spectroscopy results examined the occurrence of bioactive functional groups required for the reduction of copper ions. X-ray diffraction (XRD) spectra confirmed the copper oxide nanoparticles crystalline nature. Furthermore, colloidal copper oxide nanoparticles effectively degrade the Coomassie brilliant blue R-250 dye beneath the sunlight.

Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV-vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent.

Romidepsin induces cell cycle arrest, apoptosis, histone hyperacetylation and reduces matrix metalloproteinases 2 and 9 expression in bortezomib sensitized non-small cell lung cancer cells

Histone deacetylase (HDAC) inhibitors have been proven to be effective therapeutic agents to kill cancer cells through inhibiting HDAC activity or altering the structure of chromatin. We recently reported that chemotherapy by the HDAC inhibitor, romidepsin activates the anti- apoptotic transcription factor NF-κB in A549 non-small cell lung cancer (NSCLC) cells and fails to induce significant levels of apoptosis. We also demonstrated that NF-κB inhibition with proteasome inhibitor bortezomib enhanced HDAC inhibitor induced mitochondrial injury and sensitize A549 NSCLC cells to apoptosis through the generation of reactive oxygen species. In this study, we investigate whether combined treatment with romidepsin and bortezomib would induce apoptosis in A549 NSCLC cells by activating cell cycle arrest, enhanced generation of p21 and p53, down-regulation of matrix metalloproteinases (MMPs) 2,9 also altering the acetylation status of histone proteins. Our data show that combination of romidepsin and bortezomib caused cell cycle arrest at Sub G0-G1 transition, up-regulation of cell cycle protein p21 and tumour suppressor protein p53. In addition, romidepsin down-regulated the expression of MMP-2,9 and hyperacetylation of histone H3 and H4 in bortezomib sensitised A549 NSCLC cells. From this study we concluded that romidepsin and bortezomib cooperatively inhibit A549 NSCLC cell proliferation by altering the histone acetylation status, expression of cell cycle regulators and MMPs. Romidepsin along with bortezomib might be an effective treatment approach for A549 NSCLC cells.

Blocking NF-κB sensitizes non-small cell lung cancer cells to histone deacetylase inhibitor induced extrinsic apoptosis through generation of reactive oxygen species.

NF-κB signalling is one of the main cell survival pathways that attenuate the anticancer efficacy of therapeutic drugs. Previous studies demonstrated that the histone deacetylase (HDAC) inhibitor induces apoptosis in some malignancies through multiple mechanisms including up-regulation of death receptors, disruption of Hsp90 function and generation of reactive oxygen species (ROS). However, HDAC inhibitor also induces a cell survival signal through NF-κB activation. In this report, we found that romidepsin, a class I HDAC inhibitor, induces NF-κB activation in A549 non-small-cell lung cancer (NSCLC) cells. We also found that inhibition of A549 cells with bortezomib (proteasome inhibitor) has blocked IκB degradation that leads to the loss of NF-κB activation and translocation which enhanced the romidepsin induced mitochondrial injury and sensitizes NSCLC cells to apoptosis. Romidepsin significantly enhances NF-κB reporter gene transcription and these effects were inhibited by bortezomib as determined by reporter gene assay. Consistently, the combined exposure of romidepsin and bortezomib reversed the effects on IκB degradation as evident with IL-8, p50 and p65 (NF-κB) expression. Apoptosis was markedly sensitized with greater ROS generation and more cell death in A549 cell lines. These events are most closely related in that bortezomib prevents the romidepsin mediated RelA acetylation and NF-κB activation, resulting in caspase activation. A strategy of blocking NF-κB activation to enhance HDAC inhibitor activity warrants further attention in NSCLC cells.

Single and double chain surfactant–cobalt(III) complexes: the impact of hydrophobicity on the interaction with calf thymus DNA, and their biological activities

Developing surfactant based metal complexes as metallodrugs is a promising approach for which it is important to know the effect of their hydrophobic tail part on the interaction with biomacromolecules as well as on their biological activities. In this report we describe some surfactant–cobalt(III) complexes differing in their tail part and the effect of hydrophobicity of these complexes on their interaction with calf thymus DNA and on the cytotoxic activities. The obtained results along with molecular docking calculations show that the single chain surfactant–cobalt(III) complexes interact with DNA via groove binding and double chain surfactant–cobalt(III) complexes interact with DNA through partial intercalation. In tune with this, double chain systems show more anticancer activity as their hydrophobic tail part makes them effectively penetrate into the cell. So, this kind of tuning of the hydrophobicity of metallodrugs will lead to optimisation of the DNA binding and cytotoxicity behaviour.

Inhibition of pathogenic bacterial growth on excision wound by green synthesized copper oxide nanoparticles leads to accelerated wound healing activity in Wistar Albino rats

An impaired wound healing is one of the major health related problem in diabetic and non-diabetic patients around the globe. The pathogenic bacteria play a predominant role in delayed wound healing, owing to interaction in the wound area. In our previous work we developed green chemistry mediated copper oxide nanoparticles using Ficus religiosa leaf extract. In the present study we make an attempt to evaluate the anti-bacterial, and wound healing activity of green synthesized copper oxide nanoparticles in male Wistar Albino rats. The agar well diffusion assay revealed copper oxide nanoparticles have substantial inhibition activity against human pathogenic strains such as Klebsiella pneumoniae, Shigella dysenteriae, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli, which were responsible for delayed wound healing process. Furthermore, the analyses results of wound closure, histopathology and protein profiling confirmed that the F. religiosa leaf extract tailored copper oxide nanoparticles have enhanced wound healing activity in Wistar Albino rats.Graphical Abstract

Diagnostic Potential of Extracellular MicroRNA in Respiratory Diseases

Lack of markers of subclinical disease state and clinical phenotype other than pulmonary function test has made the diagnosis and interventions of environmental respiratory diseases a major challenge. MicroRNAs (miRNAs), small non-coding single stranded RNAs, have emerged as potential disease-modifier in various environmental respiratory diseases. They can also be found in various body fluids and are remarkably stable. Because of their high stability, disease-specific expression, and the ease to detect and quantify them have raised the potential of miRNAs in body fluids to be useful clinical diagnostic biomarkers for lung disease phenotyping. In the present review, we provide a comprehensive overview of progress made in identifying miRNAs in various body fluids including blood, serum, plasma, bronchoalveolar lavage (BAL) fluid, and sputum as biomarkers for a wide range of human respiratory diseases such as acute lung injury/acute respiratory distress syndrome (ALI/ARDS), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and asthma. Finally, we discuss several challenges remain to be concerned and suggest few disease-specific and non-specific miRNAs to become part of future clinical practice.

Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer.

The biodegradable polymeric nanoparticles have been potentially used to carry various chemotherapy agents into cancer cells for targeted drug delivery. Conversely, the biodistribution and toxic effects of these drug-loaded nanoparticles have raised some concerns. In the present study, we tried to explore the prospective histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) loaded poly (DL-lactide-co-glycolide) (PLGA) nanoparticles biocompatibility and biodistribution in animal system. The biocompatibility of SAHA loaded PLGA nanoparticles were evaluated through hemolysis, biochemical and histopathological analysis. The analysis results showed SAHA loaded PLGA nanoparticles has good hemocompatibility, not at all an elevation of blood biochemical parameters and no specific remarkable tissues changes in liver, kidney, lung, and heart as compared with control. The orally administered SAHA loaded PLGA nanoparticles distributions in various organs were confirmed using spectrofluorometry and fluorescence microscope. The results shows nanoparticles were remained detectable in the liver, kidney, heart and lung tissues after 3days. Moreover, the SAHA loaded PLGA nanoparticles are actively taken up in the A549 lung cancer cells. The overall results conclude that the histone deacetylase inhibitor SAHA loaded PLGA nanoparticles is biocompatible and actively distributed various organs in the animal system. The biocompatible SAHA loaded PLGA nanoparticles may be a suitable anticancer agent in the near feature.

Anticancer activity of graphene oxide-reduced graphene oxide-silver nanoparticle composites

In the present study, a chemical route was employed to synthesize graphene oxide (GO)-reduced graphene oxide (rGO)-Ag nanoparticle (AgNP) composites from graphite and AgNO3 using vitamin C as reducing agent. Powder X-ray diffraction pattern and field emission scanning electron microscope images revealed that the AgNP were uniformly distributed on the surface of GO and rGO nanosheets. For the first time, the cytotoxicity of GO, rGO, AgNP, GO-AgNP and rGO-AgNP composites were examined against human lung cancer A549 cells using MTT assay and reported quantitatively. The rGO-AgNP showed significant cytotoxicity activity with an IC50 value of 30μg/mL towards A549 cells which is higher than that of GO (180μg/mL), rGO (160μg/mL) and GO-AgNP (100μg/mL). Compared to AgNP (6μg/mL), rGO-AgNP shows partial agglomeration of AgNP on rGO sheets, which reduces the interaction between rGO-AgNP and A549 cells leading to lesser anticancer activity than AgNP. The interaction between rGO and AgNP leads to increase in the material biocompatibility, reducing the toxicity and corrosive characteristic.