Goyang, South Korea
Goyang, South Korea

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Park K.-S.,Sungkyunkwan University | Park K.-S.,Samsung | Tae J.,Yonsei University | Choi B.,Sungkyunkwan University | And 12 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2010

Live imaging is a powerful technique that can be used to characterize the fate and location of stem cells in animal models. Here we investigated the characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, MNPs@SiO2(RITC). We also conducted various in vivo-uptake tests with nanoparticle-labeled human MSCs. MNPs@SiO2(RITC) showed photostability against ultraviolet light exposure and were nontoxic to human MSCs, based on the MTT, apoptosis, and cell cycle arrest assays. In addition, MNPs@SiO2(RITC) did not affect the surface phenotype or morphology of human MSCs. We also demonstrated that MNPs@SiO2(RITC) have stable retention properties in MSCs in vitro. Furthermore, using optical and magnetic resonance imaging, we successfully detected a visible signal from labeled human MSCs that were transplanted into NOD.CB17-PrkdcSCID (NOD-SCID) mice. These results demonstrate that MNPs@SiO2(RITC) are biocompatible and useful tools for human MSC labeling and bioimaging. From the Clinical Editor: The characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, RITC were investigated in this study. RITC showed photostability against ultraviolet light exposure and was nontoxic to human MSCs. Using both optical and magnetic resonance imaging, successful detection of signal from labeled human MSCs transplanted into mice is demonstrated. © 2010 Elsevier Inc. All rights reserved.


Kim J.S.,Biterials Co. | Kim Y.-H.,Seoul National University | Kim Y.-H.,Cancer Research Institute | Kim J.H.,Biterials Co. | And 16 more authors.
Nanomedicine | Year: 2012

Aim: To monitor cells in vivo or to detect the sentinel lymph node, we developed a PET/MRI silica nanoprobe with an enhanced near-infrared fluorescence signal. Methods: We developed enhanced near-infrared fluorescent (NIRF) magnetic silica nanoparticles, MNP-SiO 2(NIR797), that encapsulate NIRF dye in the silica. We applied this probe to visualizing cells in the deep tissue of mice using NIRF imaging. After labeling with a radioisotope, 68Ga, on the surface of MNP-SiO 2(NIR797), we injected it into the forepaw of mice to visualize the sentinel lymph node. Results: This encapsulated nanoprobe showed enhancement of fluorescent intensity and stability compared with the nanoprobe, which had the same dyes on the surface of the silica nanoparticles. We also obtained multimodal in vivo imaging of 68Ga-{MNP-SiO 2(NIR797)} applied to sentinel lymph node detection of mice using PET/MRI/NIRF images. Conclusion: This multimodal nanoprobe with enhanced fluorescence may provide a useful tool for imaging diagnostics and cell tracking. © 2012 Future Medicine Ltd.


Jeong H.,Gwangju Institute of Science and Technology | Jeong H.,Chonbuk National University | Kim Y.H.,Sungkyunkwan University | Seo T.H.,Chonbuk National University | And 4 more authors.
Optics Express | Year: 2012

We report on the efficiency enhancement in GaN-based lightemitting diodes (LEDs) using ZnO micro-walls grown by a hydrothermal method. The formation of ZnO micro-walls at the indium tin oxide (ITO) border on the LED structure is explained by the heterogeneous nucleation effect. The light output power of LEDs with ZnO micro-walls operated at 20 mA was found to increase by approximately 30% compared to conventional LEDs. Moreover, the finding of nearly the same current-voltage characteristics of GaN-based LEDs with and without a ZnO microwall shows that the ZnO micro-wall does not influence the electrical properties of the device but only leads to an increase in the light extraction efficiency. From the confocal scanning electroluminescence results, we confirm that ZnO micro-walls enhance the light output power via the photon wave-guiding effect. © 2012 Optical Society of America.


Choi E.-S.,Chonbuk National University | Chung T.,Joongbu University | Kim J.-S.,Biterials Co. | Lee H.,Seoul National University | And 3 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2013

Mithramycin A (Mith) is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Mith inhibits myeloid cell leukemia-1 (Md-1) to induce apoptosis in prostate cancer, but the molecular mechanism underlying this process has not been fully elucidated. The aim of this study was therefore to investigate the detailed molecular mechanism related to Mith-induced apoptosis in prostate cancer cells. Mith decreased the phosphorylation of mammalian target of rapamycin (mTOR) in both cell lines overexpressing phospho-mTOR compared to RWPE-1 human normal prostate epithelial cells. Mith significantly induced truncated Bid (tBid) and siRNA-mediated knock-down of Md-1 increased tBid protein levels. Moreover, Mith also inhibited the phosphorylation of mTOR on serine 2448 and Md-1, and increased tBid protein in prostate tumors in athymic nude mice bearing DU145 cells as xenografts. Thus, Mith acts as an effective tumor growth inhibitor in prostate cancer cells through the mTOR/Md-1/ tBid signaling pathway. © 2013 JCBN.


Kim J.H.,Biterials Co | Chung H.H.,Seoul National University | Jeong M.S.,Biterials Co | Song M.R.,Biterials Co | And 2 more authors.
International Journal of Nanomedicine | Year: 2013

Ovarian cancer is the fifth-leading cause of cancer-related deaths among women as a result of late diagnosis. For survival rates to improve, more sensitive and specific methods for earlier detection of ovarian cancer are needed. This study presents the development of rapid and specific one-step circulating tumor cell (CTC) detection using flow cytometry in a whole-blood sample with fluorescent silica nanoparticles. We prepared magnetic nanoparticle (MNP)-SiO2(rhodamine B isothiocyanate [RITC]) (MNP-SiO2[RITC] incorporating organic dyes [RITC, λmax(ex/em) = 543/580 nm]) in the silica shell. We then controlled the amount of organic dye in the silica shell of MNP-SiO2(RITC) for increased fluorescence intensity to overcome the autofluorescence of whole blood and increase the sensitivity of CTC detection in whole blood. Next, we modified the surface function group of MNP-SiO2(RITC) from -OH to polyethylene glycol (PEG)/COOH and conjugated a mucin 1 cell surface-associated (MUC1) antibody on the surface of MNP-SiO2(RITC) for CTC detection. To study the specific targeting efficiency of MUC1-MNP-SiO2(RITC), we used immunocytochemistry with a MUC1-positive human ovarian cancer cell line and a negative human embryonic kidney cell line. This technology was capable of detecting 100 ovarian cancer cells in 50 μL of whole blood. In conclusion, we developed a one-step CTC detection technology in ovarian cancer based on multifunctional silica nanoparticles and the use of flow cytometry. © 2013 Kim et al, publisher and licensee Dove Medical Press Ltd.


Shin J.-A.,Chonbuk National University | Kim J.-S.,Biterials Co. | Kwon K.-H.,Gwangju University | Nam J.-S.,Gachon University | And 3 more authors.
Oncology Letters | Year: 2012

Sanguisorba officinalis L. has been used in traditional Asian medicine to treat diseases including diarrhea, chronic intestinal infections, duodenal ulcers and bleeding. This study examined the antiproliferative effects and apoptotic activity of hot water extract of S. officinalis L. (HESO) on HSC4 and HN22 human oral cancer cells. The effects of HESO were evaluated by the 3-(4,5-dimethylthiazol-20yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, 4'-6-diamidino-2-phenylindole (DAPI) staining and western blot analysis. HESO was found to inhibit cell growth and induce apoptosis in HSC4 and HN22 oral cancer cells. HESO downregulated myeloid cell leukemia-1 (Mcl-1) in HSC4 cells and was associated with the activation of Bak, resulting in Bak oligomerization on the mitochondrial outer membrane. HESO did not alter Mcl-1 expression in HN22 cells, but it decreased Sp1 expression. The downregulation of Sp1 by HESO in HN22 cells resulted in a decrease in survivin, a downstream target protein of Sp1. These results suggested that HESO inhibited the growth of oral cancer through either Mcl-1 or Sp1, indicating that HESO may serve as a potential drug candidate against oral cancer. © 2012 Spandidos Publications Ltd.


Choi E.-S.,Chonbuk National University | Kim J.-S.,Biterials Co. | Kwon K.-H.,Gwangju University | Kim H.-S.,Chonbuk National University | And 2 more authors.
Molecular Medicine Reports | Year: 2012

Sanguisorba officinalis is a natural plant that has been traditionally used for the treatment of inflammatory and metabolic diseases. Several studies have reported that its extracts exhibit anticancer, antioxidative and anti-lipid peroxidation activities. However, the effects of this plant on human prostate cancer cells have not yet been investigated. In the present study, we investigated the inhibitory effects and underlying mechanisms of a methanol extract of Sanguisorba officinalis (MESO) in PC3 human prostate cancer cells. MESO significantly decreased cell growth and induced apoptosis through the intrinsic apoptosis pathway. MESO decreased the expression levels of myeloid cell leukemia-1 (Mcl-1), a Bcl-2-like anti-apoptotic protein that is highly expressed in various cancer cell lines. Expression levels of the pro-apoptotic protein Bax were increased by MESO whereas those of Bak and Bcl-xL were unchanged. In addition, MESO induced the oligomerization of Bax in the mitochondrial outer membrane. These results suggest that MESO inhibits the growth of prostate cancer cells and induces apoptotic cell death by the downregulation of Mcl-1 protein expression and the oligomerization of Bax. Therefore, MESO has potential as a drug candidate for the treatment of prostate cancer.


PubMed | Biterials Co.
Type: Journal Article | Journal: Nanomedicine (London, England) | Year: 2012

To monitor cells in vivo or to detect the sentinel lymph node, we developed a PET/MRI silica nanoprobe with an enhanced near-infrared fluorescence signal.We developed enhanced near-infrared fluorescent (NIRF) magnetic silica nanoparticles, MNP-SiO2(NIR797), that encapsulate NIRF dye in the silica. We applied this probe to visualizing cells in the deep tissue of mice using NIRF imaging. After labeling with a radioisotope, (68)Ga, on the surface of MNP-SiO2(NIR797), we injected it into the forepaw of mice to visualize the sentinel lymph node.This encapsulated nanoprobe showed enhancement of fluorescent intensity and stability compared with the nanoprobe, which had the same dyes on the surface of the silica nanoparticles. We also obtained multimodal in vivo imaging of (68)Ga-{MNP-SiO2(NIR797)} applied to sentinel lymph node detection of mice using PET/MRI/NIRF images.This multimodal nanoprobe with enhanced fluorescence may provide a useful tool for imaging diagnostics and cell tracking.


We studied the toxicity of ZnO nanomaterials in terms of physicochemical characteristics and reactive oxygen species (ROS) properties. ZnO nanorods [synthesized at room temperature (ZnO-RT, length; 18.04.2 nm) and at 60 C (ZnO-60, length; 80.56.8 nm)] were used to evaluate the potential toxicity upon growth velocity-related particle size. The cytotoxicity of ZnO-60 was higher than that of ZnO-RT. We observed that the toxicity of ZnO-RT and ZnO-60 was related with ROS formation by using antioxidant N-acetylcysteine and electron spin resonance. Also, we found that the source of toxicity was not related to Zn(2+) ions released from ZnO in 24h treatment. Our results indicate that toxicity of ZnO nanorods is caused by the amounts of ROS. Our study strongly suggests that size of nanomaterial is not the sole factor to be considered, thus, the development of appropriate criteria based on morphological/physicochemical characteristics as well as synthesis procedures is needed to evaluate the precise toxicity.


PubMed | Biterials Co
Type: | Journal: International journal of nanomedicine | Year: 2013

Ovarian cancer is the fifth-leading cause of cancer-related deaths among women as a result of late diagnosis. For survival rates to improve, more sensitive and specific methods for earlier detection of ovarian cancer are needed. This study presents the development of rapid and specific one-step circulating tumor cell (CTC) detection using flow cytometry in a whole-blood sample with fluorescent silica nanoparticles. We prepared magnetic nanoparticle (MNP)-SiO2(rhodamine B isothiocyanate [RITC]) (MNP-SiO2[RITC] incorporating organic dyes [RITC, max(ex/em) = 543/580 nm]) in the silica shell. We then controlled the amount of organic dye in the silica shell of MNP-SiO2(RITC) for increased fluorescence intensity to overcome the autofluorescence of whole blood and increase the sensitivity of CTC detection in whole blood. Next, we modified the surface function group of MNP-SiO2(RITC) from -OH to polyethylene glycol (PEG)/COOH and conjugated a mucin 1 cell surface-associated (MUC1) antibody on the surface of MNP-SiO2(RITC) for CTC detection. To study the specific targeting efficiency of MUC1-MNP-SiO2(RITC), we used immunocytochemistry with a MUC1-positive human ovarian cancer cell line and a negative human embryonic kidney cell line. This technology was capable of detecting 100 ovarian cancer cells in 50 L of whole blood. In conclusion, we developed a one-step CTC detection technology in ovarian cancer based on multifunctional silica nanoparticles and the use of flow cytometry.

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