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      • Biocompatible magnetite nanoparticles with varying silica‐coating layer for use in biomedicine: Physicochemical and magnetic properties, and cellular compatibility

        Singh, Rajendra K.,Kim, Tae‐,Hyun,Patel, Kapil D.,Knowles, Jonathan C.,Kim, Hae‐,Won Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of biomedical materials research. Part A Vol.a100 No.7

        <P><B>Abstract</B></P><P>Magnetic nanoparticles (MNPs) are considered highly useful in therapeutic and diagnostic applications. However, MNPs require surface modification to promote dispersibility in aqueous solutions and thus biocompatibility. In this article, the authors modified MNPs with inorganic silica layer to create silica‐coated magnetite nanoparticles (MNP@Si) via sol–gel process. Synthesis involves hydrolysis and condensation steps using tetraethylorthosilicate (TEOS) in methanol/ polyethylene glycol (PEG) solution and ammonia catalyst. Nanoparticles were characterized in terms of morphology, particle size, crystalline phase, chemical‐bond structure, surface charge and magnetic properties: in particular, the MNP@Si size was easily tunable through alteration of the Fe<SUB>3</SUB>O<SUB>4</SUB>‐to‐TEOS ratio. As this ratio increased, the MNP@Si size decreased from 270 to 15 nm whilst maintaining core 12‐nm MNP particle size, indicating decrease in thickness of the silica coating. All MNP@Si, in direct contrast to uncoated MNPs, showed excellent stability in aqueous solution. The particles' physicochemical and magnetic properties systematically varied with size (coating thickness), and the zeta potential diminished toward negative values, while magnetization increased as the coating thickness decreased. 15‐nm MNP@Si showed excellent magnetization (about 64.1 emu/g), almost comparable to that of uncoated MNPs (70.8 emu/g). Preliminary <I>in vitro</I> assays confirmed that the silica layer significantly reduced cellular toxicity as assessed by increase in cell viability and reduction in reactive oxygen species production during 48 h of culture. Newly‐developed MNP@Si, with a high capacity for magnetization, water‐dispersibility, and diminished cell toxicity, may be potentially useful in diverse biomedical applications, including delivery of therapeutic and diagnostic biomolecules. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.</P>

      • Mesoporous silica-layered biopolymer hybrid nanofibrous scaffold: a novel nanobiomatrix platform for therapeutics delivery and bone regeneration.

        Singh, Rajendra K,Jin, Guang-Zhen,Mahapatra, Chinmaya,Patel, Kapil D,Chrzanowski, Wojciech,Kim, Hae-Won American Chemical Society 2015 ACS APPLIED MATERIALS & INTERFACES Vol.7 No.15

        <P>Nanoscale scaffolds that characterize high bioactivity and the ability to deliver biomolecules provide a 3D microenvironment that controls and stimulates desired cellular responses and subsequent tissue reaction. Herein novel nanofibrous hybrid scaffolds of polycaprolactone shelled with mesoporous silica (PCL@MS) were developed. In this hybrid system, the silica shell provides an active biointerface, while the 3D nanoscale fibrous structure provides cell-stimulating matrix cues suitable for bone regeneration. The electrospun PCL nanofibers were coated with MS at controlled thicknesses via a sol-gel approach. The MS shell improved surface wettability and ionic reactions, involving substantial formation of bone-like mineral apatite in body-simulated medium. The MS-layered hybrid nanofibers showed a significant improvement in mechanical properties, in terms of both tensile strength and elastic modulus, as well as in nanomechanical surface behavior, which is favorable for hard tissue repair. Attachment, growth, and proliferation of rat mesenchymal stem cells were significantly improved on the hybrid scaffolds, and their osteogenic differentiation and subsequent mineralization were highly up-regulated by the hybrid scaffolds. Furthermore, the mesoporous surface of the hybrid scaffolds enabled the loading of a series of bioactive molecules, including small drugs and proteins at high levels. The release of these molecules was sustainable over a long-term period, indicating the capability of the hybrid scaffolds to deliver therapeutic molecules. Taken together, the multifunctional hybrid nanofibrous scaffolds are considered to be promising therapeutic platforms for stimulating stem cells and for the repair and regeneration of bone.</P>

      • Progress in Nanotheranostics Based on Mesoporous Silica Nanomaterial Platforms

        Singh, Rajendra K.,Patel, Kapil D.,Leong, Kam W.,Kim, Hae-Won American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.12

        <P>Theranostics based on nanoparticles (NPs) is a promising paradigm in nanomedicine. Mesoporous silica nanoparticle (MSN)-based systems offer unique characteristics to enable multimodal imaging or simultaneous diagnosis and therapy. They include large surface area and volume, tunable pore size, functionalizable surface, and acceptable biological safety. Hybridization with other NPs and chemical modification can further potentiate the multifunctionality of MSN-based systems toward translation. Here, we update the recent progress on MSN-based systems for theranostic purposes. We discuss various synthetic approaches used to construct the theranostic platforms either via intrinsic chemistry or extrinsic combination. These include defect generation in the silica structure, encapsulation of diagnostic NPs within silica, their assembly on the silica surface, and direct conjugation of dye chemicals. Collectively, in vitro and in vivo results demonstrate that multimodal imaging capacities can be integrated with the therapeutic functions of these MSN systems for therapy. With further improvement in bioimaging sensitivity and targeting specificity, the multifunctional MSN-based theranostic systems will find many clinical applications in the near future.</P>

      • C-Dot Generated Bioactive Organosilica Nanospheres in Theranostics: Multicolor Luminescent and Photothermal Properties Combined with Drug Delivery Capacity

        Singh, Rajendra K.,Patel, Kapil D.,Mahapatra, Chinmaya,Kang, Min Sil,Kim, Hae-Won American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.37

        <P>Biocompatible nanomaterials that allow for labeling cells and tissues with the capacity to load and deliver drug molecules hold great promise for the therapeutic-diagnostic purposes in tissue repair and disease cure. Here,a novel nanoplatform, called C-dot Bioactive organosilica nanosphere (C-BON), is introduced to have excellent theranostic potential, such as controlled 'drug delivery., visible-light imaging, and NIR photothermal activity. C-dots with a few nanometers were in situ generated in the Ca-containing organosilica mesoporous nanospheres through the sol-gel and thermal-treatment processes. The C-BON exhibited multicolor luminescence over a wide visible-light range with Strong emissions and high photostability over time and against acidity and the possible in vivo optical imaging capacity when injected in rat subcutaneous tissues. Moreover, the C-BON showed a photothermal heating effect upon the irradiation of near-infrared. The C-BON) thanks to the high mesoporoSity and existence of Ca2+ ions,demonstrated excellent loading capacity of anticancer drug doxorubicin (as high as 90% of carrier weight), and long-term (over a couple of weeks) and pH/NIR-dependent release ability. The C-BON preserved the compositional merit of Ca-Si glass, having excellent bioactivity and tell compatibility in vitro. Taken all, the multifunctional properties of C-BON-multicolor luminescence, photothermal activity, and high drug loading and controlled release together with its excellent bioactivity and cell compatibility potentiate the future applications' in theranostics (chemotherapy and photothermal therapy with optical imaging).</P>

      • Multifunctional Hybrid Nanocarrier: Magnetic CNTs Ensheathed with Mesoporous Silica for Drug Delivery and Imaging System

        Singh, Rajendra K.,Patel, Kapil D.,Kim, Jung-Ju,Kim, Tae-Hyun,Kim, Joong-Hyun,Shin, Ueon Sang,Lee, Eun-Jung,Knowles, Jonathan C.,Kim, Hae-Won American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.4

        <P>Here we communicate the development of a novel multifunctional hybrid nanomaterial, magnetic carbon nanotubes (CNTs) ensheathed with mesoporous silica, for the simultaneous applications of drug delivery and imaging. Magnetic nanoparticles (MNPs) were first decorated onto the multiwalled CNTs, which was then layered with mesoporous silica (<I>m</I>SiO<SUB>2</SUB>) to facilitate the loading of bioactive molecules to a large quantity while exerting magnetic properties. The hybrid nanomaterial showed a high mesoporosity due to the surface-layered <I>m</I>SiO<SUB>2</SUB>, and excellent magnetic properties, including magnetic resonance imaging in vitro and in vivo. The mesoporous and magnetic hybrid nanocarriers showed high loading capacity for therapeutic molecules including drug gentamicin and protein cytochrome C. In particular, genetic molecule siRNA was effectively loaded and then released over a period of days to a week. Furthermore, the hybrid nanocarriers exhibited a high cell uptake rate through magnetism, while eliciting favorable biological efficacy within the cells. This novel hybrid multifunctional nanocarrier may be potentially applicable as drug delivery and imaging systems.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2014/aamick.2014.6.issue-4/am4056936/production/images/medium/am-2013-056936_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am4056936'>ACS Electronic Supporting Info</A></P>

      • KCI등재
      • Combinatory Cancer Therapeutics with Nanoceria-Capped Mesoporous Silica Nanocarriers through pH-triggered Drug Release and Redox Activity

        Singh, Rajendra K.,Patel, Kapil D.,Mahapatra, Chinmaya,Parthiban, S. Prakash,Kim, Tae-Hyun,Kim, Hae-Won American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.1

        <P>In the field of nanomedicine, drug-loaded nanocarriers that integrate nanotechnology and chemotherapeutics are widely used to achieve synergistic therapeutic effects. Here, we prepared mesoporous silica nanoparticles capped with cerium oxide nanoparticles (COP@MSN) wherein a pH trigger-responsive mechanism was used to control drug release and intracellular drug delivery. We blocked the mesopores of the carboxyl-functionalized MSN with aminated COP. These pores could be opened in acidic conditions to release the loaded drug, thus establishing a pH-responsive drug release system. We loaded doxorubicin (DOX) as anticancer biomolecule into the pores of MSN and capped with COP. The COP@DOX-MSN system showed a typical drug release profile in an acidic medium, which, however, was not observed in a neutral medium. In vitro studies using cancer cell line (HeLa) proved that the COP@DOX-MSN entered efficiently into HeLa cells and released DOX to the level sufficient for cytotoxicity. The cytotoxic effect of COP in cancer cells was facilitated by the pro-oxidant property of COPs, which considerably raised the reactive oxygen species (ROS) level, thereby leading to cellular apoptosis. The combination of DOX with COP (COP@DOX-MSN) showed even higher ROS level, demonstrating a cytotoxic synergism of drug and nanoparticle in terms of ROS generation. Collectively, the COP@DOX-MSN is considered useful for cancer treatment with the combined capacity of pH-controlled drug delivery, chemotherapeutics, and redox activity.</P> [FIG OMISSION]</BR>

      • SCIESCOPUSKCI등재

        Carbon Fibres for the Repair of Abdominal Wall Defects in Rabbits

        A.K. Gangwar,A.K. Sharma,Naveen Kumar,S.K. Maiti,N. Kumar,O.P. Gupta,T.K. Goswami,Rajendra Singh 한국탄소학회 2005 Carbon Letters Vol.6 No.1

        Sixteen clinically healthy New Zealand white rabbits of either sex were divided into two equal groups I and II of 8 animals each. Under thiopental sodium (2.5%) anaesthesia a linear full thickness abdominal wall defect of 3 cm in length was created and repaired with continuous suture pattern using 3000 filaments of carbon fibres and 1~0 black braided nylon suture, ingroup I and II respectively. Increased vascularity was observed in carbon fibres (group I) and on day 30 the carbon fibres were covered by white fibrous tissue. Significantly higher (P < 0.05) values of glucose was seen on day 14 in group I, whereas, decrease in glucose value was observed in group II. Histopathologically, the carbon fiber implant induced extensive fibrous tissue (collagen fiber) reaction. Negligible inflammatory cells in the stroma indicate the host tissue tolerance to carbon fibers. Histochemically, gradually increased alkaline phosphatase activity up to day 14 in group I, suggested the proliferation of fibroblasts in early stages.

      • SCIESCOPUSKCI등재

        Carbon Fibres for the Repair of Abdominal Wall Defects in Rabbits

        Gangwar, A.K.,Sharma, A.K.,Kumar, Naveen,Maiti, S.K.,Kumar, N.,Gupta, O.P.,Goswami, T.K.,Singh, Rajendra Korean Carbon Society 2005 Carbon Letters Vol.6 No.1

        Sixteen clinically healthy New Zealand white rabbits of either sex were divided into two equal groups I and II of 8 animals each. Under thiopental sodium (2.5%) anaesthesia a linear full thickness abdominal wall defect of 3 cm in length was created and repaired with continuous suture pattern using 3000 filaments of carbon fibres and 1~0 black braided nylon suture, ingroup I and II respectively. Increased vascularity was observed in carbon fibres (group I) and on day 30 the carbon fibres were covered by white fibrous tissue. Significantly higher (P < 0.05) values of glucose was seen on day 14 in group I, whereas, decrease in glucose value was observed in group II. Histopathologically, the carbon fiber implant induced extensive fibrous tissue (collagen fiber) reaction. Negligible inflammatory cells in the stroma indicate the host tissue tolerance to carbon fibers. Histochemically, gradually increased alkaline phosphatase activity up to day 14 in group I, suggested the proliferation of fibroblasts in early stages.

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