Aby Cheruvathoor Poulose

Uptake of FITC Labeled Silica Nanoparticles and Quantum Dots by Rice Seedlings: Effects on Seed Germination and Their Potential as Biolabels for Plants

The use of fluorescent nanomaterials with good photostability and biocompatibility in live imaging of cells has gained increased attention. Even though several imaging techniques have been reported for mammalian cells, very limited literatures are available for nanomaterial based live imaging in plant system. We studied the uptake ability of two different nanomaterials, the highly photostable CdSe quantum dots and highly biocompatible FITC-labeled silica nanoparticles by rice seedlings which could provide greater opportunities for developing novel in vivo imaging techniques in plants. The effects of these nanomaterials on rice seed germination have also been studied for analyzing their phytotoxic effects on plants. We observed good germination of seeds in the presence of FITC-labeled silica nanoparticles whereas germination was arrested with quantum dots. The uptake of both the nanomaterials has been observed with rice seedlings, which calls for more research for recommending their safe use as biolabels in plants.

Bacterial exopolysaccharide based nanoparticles for sustained drug delivery, cancer chemotherapy and bioimaging

Introduction of a novel biocompatible, stable, biomaterial for drug delivery application remains always challenging. In the present study, we report the synthesis of an extremophilic bacterial sulfated polysaccharide based nanoparticle as a stable biocompatible material for drug delivery, evaluation of anticancer efficacy and bioimaging. Mauran (MR), the sulfated exopolysaccharide extracted from a moderately halophilic bacterium, Halomonas maura was used for the synthesis of nanoparticles along with chitosan (CH). MR/CH nanoparticles were synthesized by simple polyelectrolyte complexation of anionic MR and cationic CH. The MR/CH hybrid nanoparticles formed were ranging between 30 and 200 nm in diameter with an overall positive zeta potential of 27.5±5 mV and was found to be stable under storage in solution for at least 8 weeks. In vitro drug release studies showed a sustained and prolonged delivery of 5-fluorouracil (5FU) for 10-12 days from MR/CH nanoparticles under three different pHs of 4.5, 6.9 and 7.4 respectively. Cytotoxicity assay revealed that MR/CH nanoparticles were non-cytotoxic towards normal cells and toxic to cancer cells. Also, 5FU loaded MR/CH nanoparticles were found more effective than free 5FU in its sustained and controlled manner of killing breast adenocarcinoma cells. Fluorescein isothiocyanate (FITC) labeled MR/CH nanoparticles were used for cell binding and uptake studies; thereby demonstrating the application of dye tagged MR/CH nanoparticles for safe and nontoxic mode of live cellular imaging. We report the introduction of an extremophilic bacterial polysaccharide, MR, for the first time as a novel biocompatible and stable biomaterial to the world of nanotechnology, pharmaceutics and biomedical technology.

Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer

BACKGROUND Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. METHODS Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. RESULTS Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. CONCLUSION The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. GENERAL SIGNIFICANCE With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.

Synthesis and application of luminescent single CdS quantum dot encapsulated silica nanoparticles directed for precision optical bioimaging

This paper presents the synthesis of aqueous cadmium sulfide (CdS) quantum dots (QDs) and silica-encapsulated CdS QDs by reverse microemulsion method and utilized as targeted bio-optical probes. We report the role of CdS as an efficient cell tag with fluorescence on par with previously documented cadmium telluride and cadmium selenide QDs, which have been considered to impart high levels of toxicity. In this study, the toxicity of bare QDs was efficiently quenched by encapsulating them in a biocompatible coat of silica. The toxicity profile and uptake of bare CdS QDs and silica-coated QDs, along with the CD31-labeled, silica-coated CdS QDs on human umbilical vein endothelial cells and glioma cells, were investigated. The effect of size, along with the time-dependent cellular uptake of the nanomaterials, has also been emphasized. Enhanced, high-specificity imaging toward endothelial cell lines in comparison with glioma cells was achieved with CD31 antibody-conjugated nanoparticles. The silica-coated nanomaterials exhibited excellent biocompatibility and greater photostability inside live cells, in addition to possessing an extended shelf life. In vivo biocompatibility and localization study of silica-coated CdS QDs in medaka fish embryos, following direct nanoparticle exposure for 24 hours, authenticated the nanomaterials’ high potential for in vivo imaging, augmented with superior biocompatibility. As expected, CdS QD-treated embryos showed 100% mortality, whereas the silica-coated QD-treated embryos stayed viable and healthy throughout and after the experiments, devoid of any deformities. We provide highly cogent and convincing evidence for such silica-coated QDs as a model nanoparticle in practice, to achieve in vitro and in vivo precision targeted imaging.

Synergistic Targeting of Cancer and Associated Angiogenesis Using Triple‐Targeted Dual‐Drug Silica Nanoformulations for Theragnostics

The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high-precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.

Biomimetic smart nanocomposite: in vitro biological evaluation of zein electrospun fluorescent nanofiber encapsulated CdS quantum dots

New hybrid quantum dot (QD)/nanofibers have potential applications in a variety of fields. A novel fluorescent nanocomposite nanofiber material, consisting of CdS and zein has been fabricated through the electrospinning process. A detailed optimization was carried out to fabricate continuous and uniform nanofibers without beads or droplets. The synthesized hybrid nanofibers were characterized by various state-of-the-art techniques such as scanning electron microscopy, transmission electron microscopy (TEM), TEM-energy dispersive spectrometry, atomic force microscopy and confocal fluorescence micrography. The optimization process was carried out to fabricate fibers ranging from 200 to 450 nm in diameter. The electrical conductivity of the zein-CdS hybrid nanofiber substrates was tested. The potential use of the electrospun CdS-encapsulated nanofibrous scaffold as substrates for cell/tissue culture was evaluated with two different cell types, i.e. mesenchymal stem cells and fibroblasts. The results showed that the electrospun fibrous scaffolds could support the attachment and the proliferation of cells. In addition, the cells cultured on the fibrous scaffolds exhibited normal cell shapes and integrated well with surrounding fibers. The obtained results confirmed the potential for the use of the electrospun QD-encapsulated fluorescent nanofiber mats as scaffolds for tissue engineering.

PEG coated biocompatible cadmium chalcogenide quantum dots for targeted imaging of cancer cells.

Cancer stands as a leading cause of mortality worldwide and diagnostics of cancer still faces drawbacks. Optical imaging of cancer would allow early diagnosis, evaluation of disease progression and therapy efficiency. To that aim, we have developed highly biocompatible PEG functionalized cadmium chalcogenide based three differently luminescent quantum dots (QDs) (CdS, CdSe and CdTe). Folate targeting scheme was utilized for targeting cancer cell line, MCF-7. We demonstrate the biocompatibility, specificity and efficiency of our nanotool in detection of cancer cells sparing normal cell lines with retained fluorescence of functionalized QDs as parental counterpart. This is the first time report of utilizing three differently fluorescent QDs and we have detailed about the internalization of these materials and time dependent saturation of targeting schemes. We present here the success of utilizing our biocompatible imaging tool for early diagnosis of cancer.

Third-order nonlinear optical properties of 3,4-ethylenedioxythiophene copolymers with chalcogenadiazole acceptors

Two 3,4-ethylenedioxythiophene (EDOT) based low band gap donor–acceptor (D–A) conjugated copolymers were designed and synthesized via direct arylation, in which the HOMO–LUMO gaps were fine-tuned by the regular insertion of electron deficient units, 2,1,3-benzothiadiazole (BTZ) and 2,1,3-benzoselenadiazole (BTSe), respectively. Structural characterization was performed by FT-IR, 1H NMR and XPS. In order to investigate the variation in the energy band structure of the copolymers, quantum-chemical calculation using density functional theory was carried out. The alternating insertion of the chalcogenadiazole unit in the PEDOT (poly(3,4-ethylenedioxythiophene)) lowers the HOMO and LUMO energy levels. As a result, the polymers with a lower band gap compared to that of the homopolymer, PEDOT, were obtained. Optical and electrochemical results confirmed that BTSe is marginally superior to BTZ in EDOT based alternate donor–acceptor copolymers. The present experimental results correlate well with HSE06 level theoretical calculations compared to those with the B3LYP level. Z-scan experiments reveal that the copolymers exhibit a strong nonlinear absorption coefficient and a nonlinear refraction coefficient of the order 10−10 esu and the third-order nonlinear susceptibility is of the order of 10−11 esu. These findings indicated that the EDOT–chalcogenadiazole copolymers can be developed into excellent third-order nonlinear optical materials.

Structurally Distinct Hybrid Polymer/Lipid Nanoconstructs Harboring a Type-I Ribotoxin as Cellular Imaging and Glioblastoma-Directed Therapeutic Vectors

A nanoformulation composed of a ribosome inactivating protein-curcin and a hybrid solid lipid nanovector has been devised against glioblastoma. The structurally distinct nanoparticles were highly compatible to human endothelial and neuronal cells. A sturdy drug release from the particles, recorded upto 72 h, was reflected in the time-dependent toxicity. Folate-targeted nanoparticles were specifically internalized by glioma, imparting superior toxicity and curbed an aggressively proliferating in vitro 3D cancer mass in addition to suppressing the anti-apoptotic survivin and cell matrix protein vinculin. Combined with the imaging potential of the encapsulated dye, the nanovector emanates as a multifunctional anti-cancer system.

Multifunctional Cu 2'x Te Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453

Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2−XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.