Nitai Debnath

Porous ZnO nanorod for targeted delivery of doxorubicin: in vitro and in vivo response for therapeutic applications

Cancer cell specific targeted delivery (TDD) by porous nanocarrier is on a high role. Here in a simple route for the synthesis of porous ZnO nanorods (ZnO) has been demonstrated. ZnO expressed very high surface area of 305.14 m2 g−1 (SBET) and uniformly distributed pores of 5 nm. In continuation ZnO has been fabricated with 3-aminophosphonic acid followed by folic acid to yield folate conjugated porous ZnO nanorod (ZnO-FA). High surface area, uniformly distributed pores on its surface make the nanocarrier suitable for high drug loading (88%) of the anticancer drug doxorubicin (DOX). A pH triggered drug release was observed with minimum release in pathophysical conditions. In vitro efficacy of DOX loaded ZnO-FA (ZnO-FA-DOX) has been evaluated against breast cancer cells MDA-MB-231, which is not possible alone by DOX or ZnO-FA. Targeted scaffold with pendant –NH2 group has been covalently bonded with fluorescent dye (RITC) for cellular uptake and imaging studies in MDA-MB-231 cells; the possible pathway for cancer regression has also been evaluated. Even in vivo acute and intravenous toxicological evaluation on murine model system complemented biocompatibility of ZnO-FA in TDD. All together we have collaged a template free synthesis of porous ZnO nanorod, successful targeting on to cancer cells, high drug loading, pH triggered drug release, in vitro efficacy of ZnO-FA-DOX against MDA-MB-231 cells and in vivo compatibility as well. We envisioned the future prospect of porous ZnO nanostructures in TDD.

Biochemical-, biophysical-, and microarray-based antifungal evaluation of the buffer-mediated synthesized nano zinc oxide: an in vivo and in vitro toxicity study.

Here we describe a simple, novel method of zinc oxide nanoparticle (ZNP) synthesis and physicochemical characterization. The dose-dependent antifungal effect of ZNPs, compared to that of micronized zinc oxide (MZnO), was studied on two pathogenic fungi: Aspergillus niger and Fusarium oxysporum. Superoxide dismutase (SOD) activity, ascorbate peroxidase activity, catalase activity, glutathione reductase (GR) activity, thiol content, lipid peroxidation, and proline content in ZNP-treated fungal samples were found to be elevated in comparison to the control, which strongly suggested that the antifungal effect of ZNPs was due to the generation of reactive oxygen species (ROS). Protein carbonylation, another marker of oxidative stress, was also evaluated by the dinitrophenyl hydrazine (DNPH) binding assay and Fourier transform infrared (FTIR) spectral analysis followed by Western blot and microarray analysis of fungal samples to confirm ROS generation by ZNPs. Micrographic studies for the morphological analysis of fungal samples (ZNP-treated and a control) exhibited an alteration in fungal morphology. The bioavailability of ZNPs on fungal cell was confirmed by energy-dispersive X-ray (EDX) analysis followed by high-resolution transmission electron microscopy (HR-TEM) and confocal microscopic analysis of the fungal samples. In vivo acute oral toxicity, acetylcholine esterase activity, and a fertility study using a mice model were also investigated for ZNPs. The long-term toxicity of ZNPs through intravenous injection was evaluated and compared to that of MZnO. The in vitro comparative toxicity of ZNPs and MZnO was evaluated on MRC-5 cells with the help of water-soluble tetrazolium (WST-1) and lactate dehydrogenase (LDH) assays. These results suggested that ZNPs could be used as an effective fungicide in modern medical and agricultural sciences.

Comparative analysis of stability and toxicity profile of three differently capped gold nanoparticles for biomedical usage

Nowadays gold nanoparticle (GNP) is increasingly being used in drug delivery and diagnostics. Here we have reported a comparative analysis of detailed stability and toxicity (in vitro and in vivo) profile of three water soluble spherical GNPs, having nearly similar size, but the surfaces of which were modified with three different capping materials aspartic acid (GNPA), trisodium citrate dihydrate (GNPC) or bovine serum albumin (GNPB). Spectral analyses on the stability of these GNPs revealed that depending on the nature of capping agents, GNPs behave differently at different environmental modalities like wide range of pH, high salt concentrations, or in solutions and buffers of biological usage. GNPB was found to be extremely stable, where capped protein molecule successfully maintained its secondary structure and helicity on the nanoparticle, whereas colloidal stability of GNPA was most susceptible to altered conditions. In vitro cytotoxicity of these nanoparticle formulations in vitro were determined by water soluble tetrazolium and lactate dehydrogenase assay in human fibroblast cell line (MRC-5) and acute oral toxicity was performed in murine model system. All the GNPs were non-toxic to MRC-5 cells. GNPC had slight hepatotoxic and nephrotoxic responses. Hepatotoxicity was also evident for GNPA treatment. Present study established that there is a correlation between capping material and stability together with toxicity of nanoparticles. GNPB was found to be most biocompatible among the three GNPs tested.

Chitosan, Carbon Quantum Dot, and Silica Nanoparticle Mediated dsRNA Delivery for Gene Silencing in Aedes aegypti: A Comparative Analysis.

In spite of devastating impact of mosquito borne pathogens on humans, widespread resistance to chemical insecticides and environmental concerns from residual toxicity limit mosquito control strategies. We tested three nanoparticles, chitosan, carbon quantum dot (CQD), and silica complexed with dsRNA, to target two mosquito genes (SNF7 and SRC) for controlling Aedes aegypti larvae. Relative mRNA levels were quantified using qRT-PCR to evaluate knockdown efficiency in nanoparticle-dsRNA treated larvae. The knockdown efficiency of target genes correlated with dsRNA mediated larval mortality. Among the three nanoparticles tested, CQD was the most efficient carrier for dsRNA retention, delivery, and thereby causing gene silencing and mortality in Ae. aegypti.

Ciprofloxacin conjugated zinc oxide nanoparticle: A camouflage towards multidrug resistant bacteria

Gradual development of antibiotic resistant bacteria is producing severe global threat. Newer strategies are now being employed in order to control the microbial infections and to reduce the mortality as well as infection rates. Herein we describe successful synthesis of ZnO nanoparticles (ZNP) under microwave assisted condition followed by functionalization with ciprofloxacin, an antibiotic, using EDC/NHS chemistry. Successful conjugation of ciprofloxacin was confirmed by FTIR spectra. Ciprofloxacin-conjugated ZnO nanoparticles (ZN-CIP) exhibited excellent antibacterial activity against clinically isolated multidrug resistant bacterial strains of Escherichia coli, Staphylococcus aureus and Klebsiella sp. ZNP were small in size with particle size distribution 18–20 nm as obtained from transmission electron microscope (TEM). Surface topology was obtained from atomic force microscopic (AFM) image and x-ray diffraction confirmed that ZNP possessed hexagonal crystal structure. A concentration of 10 µg/mL of ZN-CIP was a benchmark concentration. During evaluation of minimum inhibitory concentration (MIC) values, similar concentration of antibiotic was incapable of producing antibacterial activity.

Nanoparticles influence on expression of cell cycle related genes in Drosophila: a microarray-based toxicogenomics study

Relatively little is known regarding the interaction of nanoscale objects with dynamic complex biological systems. Microarray-based toxicogenomics studies may serve as a suitable technique to explore the genome wide effects of nanoparticles on any organism through a single experiment. The influence of nanoporous aluminosilicate nanoparticles (NP), citrate-capped gold NP, lipophilic silica NP, BSA-capped silver NP, and lipophilic zinc oxide NP were studied on 75 cell cycle-related genes of adult Drosophila melanogaster. Microarray experiments were conducted after the flies were fed with NP-mixed media for 15 days. Data showed that silver, zinc oxide, and alumino silicate NP predominantly perturbed cell cycle genes, whereas gold and silica NP exerted the least influence on these genes.

Entomotoxicity Assay of Silica, Zinc Oxide, Titanium Dioxide, Aluminium Oxide Nanoparticles on Lipaphis pseudobrassicae

High volume uses of conventional pesticides end up contaminating ground water and soil with highly toxic pesticide residues. Nano‐pesticides and nano‐encapsulated pesticides are expected to reduce the volume of application and slow down the fast release kinetics. Nature inspired Diatomaceous Earth (DE) were used to design and fabricate a variety of 15–50 nm size range hydrophilic, hydrophobic and lipophilic SiO2, ZnO, TiO2 (anatase and rutile) and Al2O3 (α and γ) nanoparticles (Nanocides). Mustard aphid (Lipaphis pseudobrassicae) causes devastations on oil producing mustard crops every year in Asia. Due to several distinct adaptations present in insects, tools of Genetics, Plant breeding, Biochemistry and Transgenic technology have not been so far effective. Nano Al2O3 and amorphous nano SiO2 were found to be highly effective and nano TiO2 was moderately effective against L. pseudobrassicae. But nano Al2O3 has deleterious effects on plant growth, whereas non crystalline nano SiO2 has no such adverse effec...

Microwave synthesis of ZnO@mSiO2 for detailed antifungal mode of action study: Understanding the insights into oxidative stress

A simple chemical method has been devised for deliberate incorporation of zinc oxide nanoparticles (ZNPs) within mesoporous nanosilica (mSiO2) matrix to yield zinc oxide nanoparticles embedded in mesoporous nanosilica (ZnO@mSiO2). ZnO@mSiO2 inhibited the growth of four strains of fungi in a dose dependant manner. A series of biochemical assays revealed generation of oxidative stress from ZnO@mSiO2 for such biocidal response. We proposed transient superoxide and its subsequent conversion to H2O2 played a pivotal role behind such biocidal response as revealed from our systematic evaluation. This resulted morphological alteration of fungi through increase in number of facets, in correlation we found up-regulation in oxidative stress related genes. Bioavailability within the fungal sample was confirmed from microscopic, spectroscopic, biophysical techniques. Protein carbonylation of fungal species was the chemical outcome of such above mentioned stress and quantified by high performance liquid chromatography (HPLC) via subsequent hydrazone derivatization. Several in vitro and in vivo evaluations revealed the biocompatibility of ZnO@mSiO2. Altogether this report claims a new biocidal agent with a detailed mode of action focusing on the origin and quantification of oxidative stress through biophysical and biochemical techniques for the first time for real time applications.

Novel entomotoxic nanocides for agro-chemical industry

In recent years, pest management scientists are reappraising the use of inert dusts as alternative insecticides because of several growing problem of the conventional insecticides like cumulative environmental pollution, increasing insect resistance to them etc. The naturally occurring amorphous micron sized silica (Diatomaceous Earth), derived from fossil phytoplankton has gained enormous popularity as a physically active insecticide in the temperate countries. Here we investigated and compared the insecticidal efficacy of surface functionalized amorphous silica nanoparticle (SNP) with micron sized silica “FossilShield90.0s” on tropical army worm Spodoptera litura. S. litura is a polyphagous pest which attacks a number of crops and vegetables. All micron and nano sized silica were applied on the second instar larvae of S. litura at four dose rates with proper control. It was found that all SNPs were much more effective than “FossilShield90.0s”. Especially, hydrophilic SNP could kill all the larvae within 24 hours of the treatment. In vitro toxicity of SNPs was evaluated on MRC-5 cells with the help of water soluble tetrazolium (WST-1) and lactate dehydrogenase (LDH) assays. Unlike conventional insecticides, SNP kills the insects by causing damage to their cuticular water barrier. Insects lose water through their damaged cuticle and die because of desiccation. As this nanocide is physically active, insects are unlikely to develop resistance against it. United States Department of Agriculture has approved amorphous silica as bio safe.

Enhancement of photon absorption in the light-harvesting complex of isolated chloroplast in the presence of plasmonic gold nanosol—a nanobionic approach towards photosynthesis and plant primary growth augmentation

A strong enhancement of electromagnetic field generated through resonating surface polaritons on metal films and particles has stimulated considerable interest in diverse research fields such as photobiology as, for example, in photosynthesis. This surface plasmon resonance (SPR) of metal nanoparticles (NPs) can augment photosynthetic chemical energy production in an artificial photosynthetic model system. In this paper, the effect of three water-dispersible gold NPs (GNPs) of nearly similar size but with different surface moieties (aspartate, bovine serum albumin, and citrate capping) is experimentally shown on the photosynthetic efficiency of isolated chloroplasts of Vigna radiata. It was found that GNPs can augment photon absorption in the light-harvesting molecular complexes (LHMCs) and can cause increased distinctive optical and electronic properties. Photosynthetic light reactions like electron transport rate, photophosphorylation, and oxygen evolution rate were increased in the presence of GNPs, indicating higher photosynthetic activity. The rate of increase was dependent on the surface capping of GNPs, and it was maximum in case of citrate-capped GNP. Moreover, it was also found that these GNP-induced enhancements had positive correlation with the primary growth parameters of V. radiata.