Browsing by Author "Singh, Sunil K."
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PublicationArticle A strategy to achieve efficient dual-mode luminescence in lanthanide-based magnetic hybrid nanostructure and its demonstration for the detection of latent fingerprints(Academic Press Inc., 2017) Shahi, Praveen K.; Singh, Priyam; Singh, Akhilesh K.; Singh, Sunil K.; Rai, Shyam B.; Prakash, RajivWe have synthesized a novel inorganic-organic hybrid nanostructure (IOHN) composed of fluoride nanophosphor (NaGd0.78Er0.02Yb0.2F4) and β-diketones complex (Eu(DBM)3Phen). The Le Bail fitting of X-ray diffraction data suggests that the nanophoshor crystallizes in a hexagonal structure (P63/m space group). The TEM studies reveal that the nanophosphor and the IOHN both have average particle size of 6–8 nm. The Eu(DBM)3Phen and NaGd0.78Er0.02Yb0.2F4 show characteristic down-shifting (DS) and up-conversion (UC) emission, under UV and NIR excitation, respectively. The IOHN comprises an excellent dual-mode optical features (DS and UC) of both the phases. Energy transfer from Er3+ (doped in inorganic phase) to Eu3+ (coordinated in organic phase) clearly demonstrates for a viable coupling between both the phases. IOHN material was found to be unique for the visualization of latent fingermarks. Because of ultrafine particle size the surface to volume ratio is relatively higher which improves the attachment of particles with the fingermarks. On the other hand, the strong paramagnetic property helps to remove excess material with magnetic wand easily. These properties provide an opportunity to probe even very weak fingermarks. Notwithstanding this, the dual-mode emission is useful for the visualization of latent fingermarks on multi-color surfaces as well. © 2016 Elsevier Inc.PublicationArticle Amine-modified graphene: Thrombo-protective safer alternative to graphene oxide for biomedical applications(2012) Singh, Sunil K.; Singh, Manoj K.; Kulkarni, Paresh P.; Sonkar, Vijay K.; Grácio, José J. A.; Dash, DebabrataGraphene and its derivatives have attracted significant research interest based on their application potential in different fields including biomedicine. However, recent reports from our laboratory and elsewhere have pointed to serious toxic effects of this nanomaterial on cells and organisms. Graphene oxide (GO) was found to be highly thrombogenic in mouse and evoked strong aggregatory response in human platelets. As platelets play a central role in hemostasis and thrombus formation, thrombotoxicity of GO potentially limits its biomedical applications. Surface chemistry of nanomaterials is a critical determinant of biocompatibility, and thus differentially functionalized nanomaterials exhibit varied cellular toxicity. Amine-modified carbon nanotubes have recently been shown to possess cytoprotective action, which was not exhibited by their relatively toxic carboxylated counterparts. We, therefore, evaluated the effect of amine modification of graphene on platelet reactivity. Remarkably, our results revealed for the first time that amine-modified graphene (G-NH 2) had absolutely no stimulatory effect on human platelets nor did it induce pulmonary thromboembolism in mice following intravenous administration. Further, it did not evoke lysis of erythrocytes, another major cellular component in blood. These findings contrasted strikingly the observations with GO and reduced GO (RGO). We conclude that G-NH 2 is not endowed with thrombotoxic property unlike other commonly investigated graphene derivatives and is thus potentially safe for in vivo biomedical applications. © 2012 American Chemical Society.PublicationArticle Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen(2011) Nayak, Manasa K.; Singh, Sunil K.; Roy, Arnab; Prakash, Vivek; Kumar, Anand; Dash, DebabrataTamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signaling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet/anti-thrombotic agent. © Schattauer 2011.PublicationBook chapter Biomedical Applications of Carbon-Based Nanomaterials(Blackwell Publishing Ltd., 2013) Singh, Sunil K.; Kulkarni, Paresh P.; Dash, DebabrataCarbon-based nanomaterials and their derivatives have triggered extensive research and promise to be some of the key materials in nanotechnology. Unlike other existing materials, carbon nanomaterials have found many scientific and technological applications in diverse areas. The wide range of superior properties (mechanical, electrical, optical and thermal) that are inherent in carbon nanostructures, specifically nanotubes and graphene, and the simplicity of their structures have played an important role in the current rapid expansion of fundamental studies of these materials and their potential use in nanotechnology. Based on their novel electronic and optical properties and their controllable chemical functionality, carbon nanostructures are expected to be used in several applications, including nanoelectronics and energy research, as well as biomedical areas such as biosensors, cellular imaging, drug delivery, photothermal therapy and diagnostics. Realizing the immense potential of carbon nanomaterials for applications in biology and medicine, we shall review recent advances in this field and discuss the outlook for the future. © 2013 John Wiley & Sons, Ltd.PublicationBook chapter Biomedical Applications of Nanomaterials: An Overview(Blackwell Publishing Ltd., 2013) Singh, Sunil K.; Kulkarni, Paresh P.; Dash, DebabrataWithin the short span of a decade, nanotechnology has evolved into a truly interdisciplinary field undergoing rapid expansion, with the promise of new developments in every traditional scientific discipline. At the nanometer scale, the self-ordering forces and properties of materials seem to be different from those at the macroscale. The application of nanotechnology in biomedical fields is one of the major thrust areas that are currently gaining momentum, as all biological systems embody the principles of nanotechnology. The nanoscience tools that are currently well understood and those that will be developed in future are likely to have an enormous impact on biology, biotechnology, and medicine. The comparable size scale of nanomaterials and biological materials, such as antibodies and proteins, facilitates their use in biological and medical applications. The biomedical community has recently discovered that the distinctive physical characteristics of nanomaterials, such as their extraordinarily high surface area to volume ratio, tuneable optical emission, unique electrical and magnetic behavior, and other novel properties can be exploited in a wide spectrum of biomedical utilities ranging from drug delivery to biosensors. Realizing the immense potential of nanomaterials for applications in diverse areas of biology and medicine, we review recent advances in this field and discuss future perspectives. © 2013 John Wiley & Sons, Ltd.PublicationArticle Characterization of antiplatelet properties of silver nanoparticles(2009) Shrivastava, Siddhartha; Bera, Tanmay; Singh, Sunil K.; Singh, Gajendra; Ramachandrarao, P.; Dash, DebabrataThrombotic disorders have emerged as serious threat to society. As anticoagulant and thrombolytic therapies are usually associated with serious bleeding complications, the focus has now shifted to regulating and maintaining platelets in an inactive state. In the present study we show that nanosilver has an innate antiplatelet property and effectively prevents integrin-mediated platelet responses, both in vivo and in vitro, in a concentration-dependent manner. Ultrastructural studies show that nanosilver accumulates within platelet granules and reduces interplatelet proximity. Our findings further suggest that these nanoparticles do not confer any lytic effect on platelets and thus hold potential to be promoted as antiplatelet/antithrombotic agents after careful evaluation of toxic effects. © 2009 American Chemical Society.PublicationArticle Characterization of graphene oxide by flow cytometry and assessment of its cellular toxicity(2011) Singh, Sunil K.; Singh, Manoj K.; Nayak, Manasa K.; Kumari, Sharda; Graćio, José J. A.; Dash, DebabrataBecause of its unique physicochemical properties, graphene oxide (GO) has found significant applications in a wide spectrum of biomedical utilities. In the present report, we have presented flow cytometry as an alternative tool for analysis of size distribution and intrinsic fluorescence of GO sheets, its interaction with cells and cytotoxicity evaluations. Copyright © 2011 American Scientific Publishers All rights reserved.PublicationArticle CNT induced β-phase in polylactide: Unique crystallization, biodegradation, and biocompatibility(2013) Singh, Narendra K.; Singh, Sunil K.; Dash, Debabrata; Gonugunta, Prasad; Misra, Manjusri; Maiti, PralayThe effect of multi-walled carbon nanotube (MWCNT) on the crystal structure, unique crystallization, mechanical behavior, enzymatic degradation, and significant improvement in biocompatibility of polylactide (PLA) nanohybrid has been reported. Functionalization of carbon nanotube using stearyl alcohol has been carried out and has been confirmed through FTIR and Raman spectroscopy. PLA nanohybrids have been synthesized using functionalized and neat MWCNT through solution route, and the improved level of dispersion of MWCNT has been achieved in PLA matrix. High-magnification transmission electron microscope images indicate the unique adsorption of PLA chain leading to the crystallization of β-phase structure on the surface of the functionalized MWCNT against the usual crystallized α-form of pure PLA. The presence of β phase in nanohybrids has been confirmed through electron diffraction pattern, differential scanning calorimetry thermograms, and X-ray diffraction patterns. The improved and diverse mechanical, thermal properties, and crystallization kinetics have been explored with the special emphasis on the relaxation behavior of β phase in dynamic mechanical analysis. The cause of these developments has been appraised from the interaction point of view as calculated from the interaction parameter (χ) using melting-point depression technique. The rate of biodegradation has been studied in detail with plausible mechanism in Proteinase K enzyme media showing their specificity and tuning of biodegradation rate followed by their optimization. For biomedical applications, the effect of pure polymer and nanohybrids on circulating blood cells has been evaluated in detail, and the hemocompatible nature of the nanohybrids has been revealed, suppressing the cellular toxicity of MWCNT. © 2013 American Chemical Society.PublicationArticle Effect of silver nanoparticles on growth of eukaryotic green algae(Shanghai Jiaotong University, 2012) Dash, Anjali; Singh, Anand P.; Chaudhary, Bansh R.; Singh, Sunil K.; Dash, DebabrataSilver nanoparticles, endowed with powerful antimicrobial property, are the most widely used nanomaterial in consumer products, with associated risk of their easy access to environment and freshwater ecosystems by surface runoff. Although toxic effects of nanosilver on bacterial, fungal and mammalian cells have been documented, its impact on algal growth remains unknown. Pithophora oedogonia and Chara vulgaris are predominant members of photosynthetic eukaryotic algae, which form major component of global aquatic ecosystem. Here we report for the first time that nanosilver has significant adverse effects on growth and morphology of these filamentous green algae in a dose-dependent manner. Exposure of algal thalli to increasing concentrations of silver nanoparticles resulted in progressive depletion in algal chlorophyll content, chromosome instability and mitotic disturbance, associated with morphological malformations in algal filaments. SEM micrographs revealed dramatic alterations in cell wall in nanoparticle-treated algae, characterized with cell wall rupture and degradation in Pithophora. Although these observations underscore severe deleterious effects of nanosilver on aquatic environment, the information can also be exploited as a bioengineering strategy to control unwanted and persistent growth of noxious algal weeds that clog the municipal water supply and water channels and produce fouling of water bodies.PublicationArticle Graphene oxide as a sustainable metal and solvent free catalyst for dehydration of fructose to 5-HMF: A new and green protocol(Elsevier B.V., 2018) Shaikh, Melad; Singh, Sunil K.; Khilari, Santimoy; Sahu, Mahendra; Ranganath, Kalluri V.S.The metal free catalytic dehydration of fructose to 5-hydroxymethylfurfural (5-HMF) using graphene oxide catalyst is reported. The reaction has been employed under solvent free condition with high reactivity and selectivity. The metal free catalyst, graphene oxide was characterized by FTIR, XRD, TEM, and Raman spectroscopy. © 2017 Elsevier B.V.PublicationArticle Graphene oxide-based biosensor for detection of platelet-derived microparticles: A potential tool for thrombus risk identification(Elsevier Ltd, 2015) Kailashiya, Jyotsna; Singh, Nitesh; Singh, Sunil K.; Agrawal, Vikas; Dash, DebabrataWe report here design of a graphene oxide-based electrochemical biosensor for detection of platelet-derived microparticles (PMPs), a major risk factor for arterial pro-thrombotic pathologies like acute myocardial infarction and stroke. Electrodes were fabricated with immobilized layers of graphene oxide and a specific antibody targeted against active conformation of integrin αIIbβ3 on PMP surface. Results showed progressive rise in impedance in Nyquist plots with increasing number of PMPs in analyte. The sensor was highly specific for PMPs and did not identify microparticles originating from other cells. Blood obtained from patients diagnosed with acute myocardial infarction exhibited significantly higher values of impedance, consistent with larger number of circulating PMPs in these patients, as compared to samples from healthy individuals, thus validating biosensor as a specific, sensitive, label-free and cost-effective tool for rapid point-of-care detection of PMPs at bedside. Our biosensor is most ideal for mass population screening programs at periphery-level healthcare units with limited resources. It is aimed at early detection of individuals having higher imminent cardiovascular risk, as well as for routine analysis, which in turn would contribute to better management and survival of screened 'high-risk' subjects. © 2014 Elsevier B.V.PublicationBook chapter Graphene oxide: Characterization by flow cytometry and biomedical applications(Nova Science Publishers, Inc., 2012) Singh, Sunil K.; Kulkarni, Paresh P.; Dash, DebabrataGraphene, a true 2-dimensional nanomaterial, has received increasing attention due to its unique physicochemical properties like large surface area, excellent conductivity, high mechanical strength and ease of bio-functionalization. Based on its unique optical, physical and electrical properties, graphene has found applications in a wide spectrum of biomedical utilities like imaging, sensing and therapeutics. Attempts are also being made to synthesize highly stable sheets of graphene, which can be easily ingested or injected into the body. Graphene can be characterized with various characterization tools like transmission electron microscopy (TEM) and atomic force microscopy (AFM). In a recent report, we have characterized graphene oxide (GO) sheets by flow cytometry, which stands out as a remarkable and versatile means for study of physical properties of graphene and graphene-cell interactions. Flow cytometry also provides rapid access to high-dimension statistical information on individual GO sheets that is not achievable with existing characterization tools. This review discusses latest advancements in graphene research highlighting its unique characteristics, potential biomedical applications, future prospective, as well as toxicity considerations. © 2012 Nova Science Publishers, Inc. All rights reserved.PublicationArticle Magnetic-field-induced Optical bistability in multifunctional Gd 2O3: Er3+/Yb3+ upconversion nanophosphor(2010) Singh, Sunil K.; Kumar, Kaushal; Srivastava, Manish K.; Rai, Devendra K.; Rai, Shyam B.The effect of an external magnetic field (0-1 T) on the upconversion emission (λexe,=976 nm) of Gd2O3 : Ers+/Yb8+ nanocrystalline phosphor has been studied. Optical bistability (hysteresis behavior in the intensity of the optical emission) for different transitions of the Er8+ ion has been observed for a complete cycle of the magnetic field between 0 and 1 T. The phosphor shows paramagnetic behavior, consistent with the presence of Gd3+ ions, at room temperature. Interaction between induced magnetization in the Gd2O3 host and the intrinsic magnetic moment of the nanosized clusters of Er3+ and Yb3+ ion pairs is proposed to be responsible for the hysteresis behavior. © 2010 Optical Society of America.PublicationArticle Nanostructure controlled anti-cancer drug delivery using poly(ε-caprolactone) based nanohybrids(2012) Singh, Narendra K.; Singh, Sunil K.; Dash, Debabrata; Das Purkayastha, Biswa Pratim; Roy, Jagat K.; Maiti, PralayWe have focused on the generation of various nanostructures of poly(ε-caprolactone) (PCL) using surface modified layered silicate. The improved and diverse mechanical, thermal and surface properties have been explored depending upon the nanostructure of the nanohybrids. The incorporation of drug into those nanohybrids further alters the nanostructure and subsequent properties. The rate of biodegradation has been studied in detail, with plausible mechanisms in different enzyme media being suggested, their specificity and the tunability of the biodegradation rate was demonstrated, followed by their optimization. The scaffolds of PCL and its nanohybrids with and without drugs have been prepared through electrospinning to control the dimensions of the nanofibers and their controlled degradation. The in-depth studies of the biocompatibility in terms of cell adhesion, genotoxicity and hemocompatibility have been performed to verify the suitability of the nanohybrids for potential biomedical applications. The biocompatibility of the nanohybrids at the gene level has been tested by the subcellular localization of an important regulator of pro-apoptotic signalling cascade, HIPK2 in human epithelial cells, demonstrating the attuned nature of the particles under study within the biological system. The blood compatibilities of the pure PCL and its nanohybrids were studied by platelet aggregation, platelet adhesion, and in vitro hemolysis assay, elucidating the excellent hemocompatibility of the novel nanohybrids. Biocompatible and hemocompatible nanohybrids have been testified for drug delivery and show sustained and controlled release of anti-cancer drugs (dexamethasone) in the presence of two dimensional disc-like nanoparticles. Hence, the developed nanohybrids are a potential biomaterial, suitable for tissue engineering and drug delivery. © 2012 The Royal Society of Chemistry.PublicationArticle Negative regulation of fibrin polymerization and clot formation by nanoparticles of silver(2011) Shrivastava, Siddhartha; Singh, Sunil K.; Mukhopadhyay, Avijit; Sinha, Akhoury S.K.; Mandal, Rajiv K.; Dash, DebabrataThrombolytic therapy in acute stroke has reduced ischemia; however, it is also associated with increased incidence of intracerebral hemorrhage and expanding stroke. Platelets and fibrin are the major components of thrombi. Since fibrin is available in large concentration at lesion sites and in all types of thrombi, it is an obvious target for majority of antithrombotic therapies. Previously we have demonstrated innate antiplatelet properties with nanosilver. It can effectively prevent platelet activation in response to physiological agonists, under both in vitro as well as ex vivo conditions, and immobilize and stabilize proteins. Here we report for the first time that nanosilver can significantly retard fibrin polymerization kinetics both in pure and plasma-incorporated systems and hence can impede thrombus formation. We also discuss the conformational changes ensued upon fibrinogen following interaction with nanosilver. Together with its inherent antiplatelet and antibacterial properties, capacity to inhibit fibrin polymerization can open up possibilities of newer biomedical application and research potential involving silver nanoparticles. © 2010 Elsevier B.V.PublicationArticle Novel microfilaricidal activity of nanosilver(2012) Singh, Sunil K.; Goswami, Kalyan; Sharma, Richa D.; Reddy, Maryada V.R.; Dash, DebabrataPurpose: The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. Methods: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. Results: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 μM, which was higher than the recorded complete inhibitory concentration value (50.6 μM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. Conclusion: The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.PublicationArticle Self-assembled aliphatic chain extended polyurethane nanobiohybrids: Emerging hemocompatible biomaterials for sustained drug delivery(Elsevier Ltd, 2014) Mishra, Abhinay; Singh, Sunil K.; Dash, Debabrata; Aswal, Vinod K.; Maiti, Biswajit; Misra, Manjusri; Maiti, PralayNovel polyurethanes (PUs) have been synthesized using an aliphatic diisocyanate and aliphatic chain extenders with varying chain length. Nanocomposites of PUs have been prepared by dispersing 2-D nanoclay in poly-ol followed by prepolymerization and subsequent chain extension using various chain extenders. Systematic improvement in toughness and adequate enhancement in stiffness in the presence of nanoclay has been observed for PUs with longer chain extenders, and these new classes of nanocomposites exhibit no toughness-stiffness trade-off. Bottom-up self-assembly starting from the molecular level to micron-scale crystallite has been revealed through electronic structure calculation, X-ray diffraction, small-angle neutron scattering, atomic force microscopy and optical images. The role of hydrogen bonding has been revealed for this type of supramolecular assembly, and in the presence of organically modified nanoclay hydrogen bonding contributes to the formation of bigger clusters of nanocomposites. Controlled biodegradation of PU and its nanocomposites has been investigated in enzymatic media. Biocompatibility of these novel nanocomposites has been extensively verified through platelet adhesion, aggregation and hemolysis assay. Sustained drug delivery by biocompatible pristine PU and its nanocomposites has been demonstrated either by controlling the crystallite size of the polyurethane through alteration of the aliphatic chain length of the extender or by incorporating disc-like nanoclay, creating a tortuous path that results in delayed diffusion. Hence, the developed nanohybrids are potential biomaterials for tissue engineering and drug delivery. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.PublicationArticle Size distribution analysis and physical/fluorescence characterization of graphene oxide sheets by flow cytometry(2011) Singh, Sunil K.; Singh, Manoj K.; Nayak, Manasa K.; Kumari, Sharda; Grácio, José J.A.; Dash, DebabrataFlow cytometry is presented here as an alternative tool for analysis of size distribution and intrinsic fluorescence of graphene oxide (GO) sheets. Unlike other nanoparticles, GO sheets induced scatter signals reasonably distinct from the background noise of the system. The number of gated signals generated by the sheets was proportional to GO concentration, indicating that non-spherical particles like GO can be convincingly studied by flow cytometry. The asymmetry in forward scatter-side scatter contour plots was consistent with a non-uniform size distribution of individual sheets in the population, which contrasted with a prototype animal cell population. GO was endowed with intrinsic fluorescence detectable through the three fluorescence channels in the cytometer and allowed comparison of relative fluorescence intensities associated with individual sheets. Flow cytometry thus provides rapid access to high-dimension statistical information on individual GO sheets that is not achievable with existing characterization tools, and may prove to be an indispensable tool in graphene research. © 2010 Elsevier Ltd. All rights reserved.PublicationArticle Stabilization of protein by biocompatible nanoparticles of silver(2009) Singh, Sunil K.; Shrivastava, Siddhartha; Nayak, Manasa K.; Sinha, Akhoury S. K.; Jagannadham, Medicherla V.; Dash, DebabrataExtraordinary optical properties, biocompatibility, and chemical stability make silver nanoparticles ideal candidate for application in bio-medical field. They are stabilized by virtue of their protein conjugation property. Here we report that in addition to protein conjugation nano silver also has excellent protein stabilization property. Formation of bioconjugate with nano silver was coupled with enhanced stabilization of protein secondary and tertiary structures, thereby retaining native conformation and preventing denaturation which is a rare phenomenon with other nanomaterials. This would be of immense significance for applications of conjugated peptides where the protein functions can be utilized. Using nano silver-BSA complex as model we have characterized optimal conditions for bioconjugation and mapped protein conformational changes ensued upon formation of conjugate. Conjugated BSA showed more resistance towards thermal denaturation as compared to its native counterpart. Our approach offers promise for designing of biologically functional, stable and controllable protein-silver nanoparticle composites. Copyright © 2009 American Scientific Publishers All rights reserved.PublicationArticle Thrombus inducing property of atomically thin graphene oxide sheets(2011) Singh, Sunil K.; Singh, Manoj K.; Nayak, Manasa K.; Kumari, Sharda; Shrivastava, Siddhartha; Grácio, José J. A.; Dash, DebabrataGraphene oxide (GO), the new two-dimensional carbon nanomaterial, is extensively investigated for potential biomedical applications. Thus, it is pertinent to critically evaluate its untoward effects on physiology of tissue systems including blood platelets, the cells responsible for maintenance of hemostasis and thrombus formation. Here we report for the first time that atomically thin GO sheets elicited strong aggregatory response in platelets through activation of Src kinases and release of calcium from intracellular stores. Compounding this, intravenous administration of GO was found to induce extensive pulmonary thromboembolism in mice. Prothrombotic character of GO was dependent on surface charge distribution as reduced GO (RGO) was significantly less effective in aggregating platelets. Our findings raise a concern on putative biomedical applications of GO in the form of diagnostic and therapeutic tools where its prothrombotic property should be carefully investigated. © 2011 American Chemical Society.