D. Sakthi Kumar

Toyo University, 白山, Tōkyō, Japan

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Publications (83)229.44 Total impact

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    ABSTRACT: Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy.
    No preview · Article · Dec 2015
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    ABSTRACT: Details of a fast and sustainable bottom up process to grow large area high quality graphene films without the aid of any catalyst are reported in this paper. We used Melaleuca alternifolia, a volatile natural extract from tea tree plant as the precursor. The as-fabricated graphene films yielded a stable contact angle of 135°, indicating their potential application in very high hydrophobic coatings. The electronic devices formed by sandwiching pentacene between graphene and aluminum films demonstrated memristive behavior and hence, these graphene films could find use in non-volatile memory devices also.
    No preview · Article · Aug 2015 · Nano Letters
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    ABSTRACT: Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bio applications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well we have investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as a promising optical nanoprobe with immense futuristic bioapplications.
    Full-text · Article · Jul 2015 · Nanoscale
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    Full-text · Dataset · Apr 2015
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    ABSTRACT: Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Mar 2015 · International Journal of Biological Macromolecules
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    ABSTRACT: A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and x-ray contrast imaging systems. The folate targeted, NIRresponsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multistimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand, triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.
    Full-text · Article · Mar 2015 · Nanoscale
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    ABSTRACT: Precise control of the placement and patterning of graphene on various substrates has tremendous impact in many fields, such as nanoscale electronics, multifunctional optoelectronic devices, and molecular sensing. A one-step facile technique involving N2-plasma promotes surface modification and enhances the surface wettability of the substrate. The technique is employed to create partially hydrophilic surfaces on SiO2/Si substrate with the aid of various templates, enabling the selective deposition, alignment, and formation of patterns comprising monolayer graphene oxide (GO) sheets; it successfully uses the Langmuir–Blodgett (LB) deposition technique over a large area without the need of any sophisticated equipment. Various characterization techniques are carried out in order to understand the possible mechanism behind the pinning of the GO on the partially treated areas. It is a relatively easy and swift process that can reliably accomplish specific surface modification with high bonding strength between GO and the substrate. This technique allows the creation of patterns with controllable dimensions. For example, the thickness of the GO sheets can be controlled; this is particularly important in creating arrays and devices at wafer-scale. Being simple yet effective and inexpensive, this technique holds tremendous potential that can be exploited for numerous applications in the field of bio-nanoelectronics.
    Full-text · Article · Feb 2015 · Advanced Materials Interfaces

  • No preview · Article · Jan 2015
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    ABSTRACT: Back Cover: A multifunctional folate targeted ribotoxinpolymeric/lipid nanoformulation is used to image and specifically arrest the proliferation tendencies of human glioblastoma by additionally suppressing the anti-apoptotic survivin and membrane interaction vinculin proteins. The formulation presented by D. S. Kumar and co-workers on page 1696 could be used as a potent theranostic vector system for diverse cancer subtypes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Full-text · Article · Dec 2014 · Macromolecular Bioscience
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    ABSTRACT: Nano-hollow polymer shells, especially those polymers which are FDA approved, have captured the attention of many researchers and scientists in the field of pharmaceutical and medical therapeutics. In the field of controlled drug/gene release, nano-capsules in colloidal solutions, i.e. particles with hollow piths, play an important role in cargo encapsulation. These nanoparticles are synthesized using a variety of procedures such as emulsion polymerization, phase separation, crosslinking of micelles, inner core etching and self-assembly. Our work proposes a novel route to prepare hollow PLGA (poly (lactic-co-glycolic) acid) nanoparticles (HNPs), which showed increased drug-encapsulation and release efficiency. The simple emulsion solvent evaporation technique was adopted to synthesize nano-hollow shells of FDA approved polymer PLGA using only one organic phase. The hollow characteristics of nanoparticles were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal microscopy analysis. The particle size was analyzed by dynamic light scattering (DLS). Nanoparticles drug loading, encapsulation and release efficiency in vitro were assessed by ultraviolet spectroscopy. The developed nanoparticles were hollow and spherical in shape and approximately 80 nm in size. The drug encapsulation efficiency is 99.4% and the drug was released in a controllable manner during in vitro analysis.
    No preview · Article · Nov 2014
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    ABSTRACT: The rising consciousness about the benefits of environment friendly and biodegradable materials demand a substitute for the prevailing non-degradable and toxic materials. Towards this aspect bacterial cellulose (BC) has numerous potential applications owing to their vital properties like high biocompatibility, biodegradability, and ecofriendly nature. In the present study, we have synthesized BC using Komagataeibacter sucrofermentans strain through batch fermentation and functionalized it with sulfate groups to form bacterial cellulose sulfate (BCS) that has negligible reports so far. Using this BCS, we have synthesized a highly transparent film by drop casting method, which exhibited high optical transmittance of 90–92% in the visible wavelength range. BCS was thoroughly characterized using SEM and AFM for its surface morphology. The XPS, FTIR, TGA and XRD studies were performed to confirm the successful sulfonation, stability and crystallinity of BC and BCS. The film morphology, surface roughness and mechanical properties were monitored using SEM, AFM, and Instron universal testing machine. The results confirm smooth surface with good integrity and mechanical properties of the BCS film. Furthermore, cell viability studies confirmed the biocompatible nature of the sample. Owing to these salient features, BCS films hold tremendous potential in the field of biomedicine, optoelectronics as well as food packaging.
    Full-text · Article · Oct 2014 · Materials Express
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    ABSTRACT: 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.
    Full-text · Article · Sep 2014 · Macromolecular Bioscience
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    ABSTRACT: Curcin, a type 1 ribosome inactivating protein (RIP) is investigated here for its cellular competence on six mammalian cell lines. Cells exposed to curcin (100 μg/ml) for 72 h exhibited significant cellular metabolic arrest, with the cancer cell lines being more sensitive. The viability assessment of the cancer cells in a 3D cell culture based assay revealed highly restricted sprouting and proliferation with near to complete dead cell population. Prominent mitochondrial dysfunction, elevated reactive oxygen species levels, nuclear degeneration, structural/mechanical destabilization and suppression of defense mechanisms were imminent with the RIP treated cells. Expression levels of nuclear factor κB (NF-κB), cytoskeletal focal adhesion kinases (FAK) and vinculin were significantly diminished. Vital cellular organelles as nucleus, mitochondria and actin were severely incapacitated on RIP exposure resulting in multimodal apoptosis and necrosis. The ability of curcin to impart comprehensive shutdown of the cells, especially cancer cells, complemented with its hemocompatibility, opens up possibilities of utilizing this ribotoxin as a prospective therapeutic candidate against cancers of diverse origins.
    Full-text · Article · Jul 2014 · Scientific Reports
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    ABSTRACT: Extremophiles are the group of organisms that are far overlooked for exploring novel biomaterials in the field of material science and bionanotechnology. Extremophilic bacterial-sulfated exopolysaccharide, mauran (MR), is employed for the bioreduction and passivation of gold nanoparticles (AuNps) to enhance the biocompatibility of AuNps and used for photothermal ablation of cancer cells. Here, various concentrations of MR solution are tested for the reduction of HAuCl4 solution in the presence as well as in the absence of an external reducing agent, to produce mauran-gold nanoparticles (MRAu Nps). These biocompatible nanocomposites are treated with cancer cell lines under in vitro conditions and NIR irradiated for complete ablation. MRAu Nps-treated cancer cells on immediate exposure to infrared radiation from a femtosecond pulse laser of operating wavelength 800 nm are subjected to hyperthermia causing cell death. Biocompatible MR stabilization could fairly reduce the cytotoxicity caused by bare AuNps during biomedical applications. Application of a biocompatible polysaccharide from extremophilic bacterial origin for reduction and passivation of AuNps and used for a biomedical purpose is known to be first of its kind in bionanofusion studies.
    No preview · Article · Jul 2014 · Particle and Particle Systems Characterization
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    ABSTRACT: The nanocrystals, so-called quantum dots (QDs), are undisputedly excellent fluorescent markers for imaging and clinical diagnostics. However, their toxicity is always a perturbing issue and remains as the major hindrance for biocompatible imaging and other biomedical applications. Here, we have demonstrated the extraction and application of an extremophilic bacterial polysaccharide, mauran (MR), from a moderately halophilic bacterium called Halomonas maura in the stabilization of ZnS:Mn2+ QDs for the first time. MR has been employed as a natural polymer for bioconjugation to enhance the cellular acceptance and decrease the cytotoxicity of QDs while being used as a fluorescent marker for imaging purposes. Five nanometer-sized QDs were stabilized using an aqueous MR solution under ambient conditions to yield 10–20 nm-sized nanoparticles. Characterization of MR-QD was performed using UV–vis and fluorescent spectroscopy, TEM, SEM, and FTIR. A cytocompatibility assay revealed that the cellular toxicity of QDs was drastically reduced on MR stabilization. In vitro cellular imaging of mouse fibroblast cells and breast adenocarcinoma cells showed that MR-QDs are equally effective as normal QD imaging without imparting any toxicity issues. Thus, it was shown that extremophilic sulfated bacterial polysaccharide, MR, can be successfully used as a novel stabilizing agent for QDs to reduce toxicity and eventually be used as a safe fluorescent agent for in vitro imaging.
    No preview · Article · Apr 2014 · ACS Sustainable Chemistry & Engineering
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    ABSTRACT: Non-specificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, dual targeted pH sensitive biocompatible polymeric nanosystem was designed and developed. ATRP based biodegradable triblock copolymer poly(polyethylene glycol methacrylate)-poly(caprolactone)-poly(polyethylene glycol methacrylate) [pPEGMA-PCL-pPEGMA] conjugated with doxorubicin via acid labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method with an average particle size of ~140 nm. Biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assay, blood compatibility studies and protein adsorption study. In vitro drug release studies showed higher doxorubicin cumulative release in pH 5.0 (~70%) as compared to that in pH 7.4 (~25%) owing to the presence of acid sensitive hydrazone linkage. Dual targeting with folate and AS1411 aptamer increased the cancer targeting efficiency of nanoparticles resulting in enhanced cellular uptake (10 fold and 100 fold increase in uptake as compared to single targeted NPs and non-targeted NPs respectively) and higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1) with subsequent higher apoptosis, while sparing normal (non-cancerous) cell line (L929) from the adverse effects of doxorubicin. The results indicate that the dual targeted pH sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers like breast, ovarian, pancreas, lung cancer etc.
    No preview · Article · Apr 2014 · Biomacromolecules
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    ABSTRACT: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks in attaining full 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. 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. Highly cyto-compatible, 10-15 nm 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. The multifunctional nanoconjugate projects its competence in imparting complete arrest on the future proliferation or migration of the cancer mass. 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.
    Full-text · Article · Dec 2013 · Biochimica et Biophysica Acta
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    ABSTRACT: Mauran (MR), a highly polyanionic sulfated exopolysaccharide was extracted from moderately halophilic bacterium; Halomonas maura and characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Purified MR was evaluated for antioxidant defense mechanisms under in vitro conditions using L929, mouse fibroblast cell line and mice liver homogenate. It was demonstrated that MR could impart protective effect against oxidative stress in both cells and tissue up to a concentration of 500μg, which is found to be safe under laboratory conditions. Various enzymatic and non-enzymatic parameters of antioxidant mechanisms were evaluated and concluded that MR has the tendency to maintain a balance of antioxidative enzymes with in the test systems studied. Also, hemocompatibility assay performed revealed that MR has a lesser hemolytic index and exhibited a prolonged clotting time, which shows both antihemolytic, and antithrombogenic nature respectively. Furthermore, absorption studies performed using fluorescent-labeled MR confirmed that MR accumulated within the cell cytoplasm neither induced cellular lysis nor affected the cell integrity.
    No preview · Article · Oct 2013 · Carbohydrate Polymers
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    ABSTRACT: Fluorinated graphene oxide (FGO) is reported for the first time as a magnetically responsive drug carrier that can serve both as a magnetic resonance imaging (MRI) and photoacoustic contrast agent, under preclinical settings, and as a type of photothermal therapy. Its hydrophilic nature facilitates biocompatibility. FGO as a broad wavelength absorber, with high charge transfer and strong non-linear scattering is optimal for NIR laser-induced hyperthermia.
    No preview · Article · Oct 2013 · Advanced Materials
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    ABSTRACT: Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, l-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions.
    No preview · Article · Oct 2013 · Journal of Magnetism and Magnetic Materials