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Daegu, South Korea

Kim H.-K.,Institute of Biomedical Engineering Research | Kim Y.-H.,Cheil Eye Research Institute | Kim T.-J.,Institute of Biomedical Engineering Research | Chang Y.,Kyungpook National University
Journal of Biomedical Nanotechnology | Year: 2016

This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponDing low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B. Copyright © 2016 American Scientific Publishers. Source

Lee E.-S.,Kyungpook National University | Jeong S.-J.,Kyungpook National University | Kim Y.-H.,Cheil Eye Research Institute | Jeon C.-J.,Kyungpook National University
Acta Histochemica et Cytochemica | Year: 2015

The present study aimed to investigate the influence of the host retinal microenvironment on cell migration and differentiation using Neuro2a (N2a) cells transduced with green fluorescent protein. N2a cells were transplanted into the vitreous cavities of developing mouse eyes (C57BL/6) on postnatal days 1, 5, and 10 (P1, 5, and 10). To analyze the effects of the host microenvironment on neural differentiation of N2a cells in vitro, cells were treated with a conditioned medium (CM) collected from retinal cells cultured at each developmental stage. We observed that numerous cells transplanted into P5 mice eyes migrated into all layers of the host retina, and the presence of processes indicated morphological differentiation. Some transplanted N2a cells expressed several neural markers. However, cells transplanted into the P1 and 10 mice eyes only proliferated within the vitreous cavity. Neurite length increased in N2a cells treated with CM collected from the cultured retinal cells from P5 and 10 mice, while western blotting revealed that the levels of proteins related to neural differentiation were not significantly altered in N2a cells treated with CM. We show that the migration and differentiation capacities of transplanted cells were differentially influenced by the microenvironment of the retinal postnatal ontogeny. © 2015 The Japan Society of Histochemistry and Cytochemistry. Source

Kim H.-K.,Kyungpook National University | Kang M.-K.,Kyungpook National University | Jung K.-H.,Kyungpook National University | Kang S.-H.,Kyungpook National University | And 5 more authors.
Journal of Medicinal Chemistry | Year: 2013

A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H 2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM -1 s-1) of the complex compare well with those of structurally analogous Gd-DOTA. The same complex is not only tumor-specific but also intracellular, enhancing MR images of cytosols and nuclei of tumor cells such as MCF-7, MDA-MB-231, and SK-HEP-1. Both DO3A-BTA and Gd(DO3A-BTA) reveal antiproliferative activities as demonstrated by GI50 and TGI values obtainable from the cell counting kit-8 (CCK-8) assays performed on these cell lines. Ex vivo and in vivo monitoring of tumor sizes provide parallel and supportive observations for such antiproliferative activities. © 2013 American Chemical Society. Source

Jung K.-H.,Kyungpook National University | Kang S.-H.,Massachusetts General Hospital | Kang M.-K.,Kyungpook National University | Kim S.,Kyungpook National University | And 7 more authors.
European Journal of Inorganic Chemistry | Year: 2015

The synthesis of two bifunctional chelates, 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) conjugates of benzothiazoles (H3L3a and H3L3b), and the corresponding gadolinium complexes (GdL3a and GdL3b) was achieved. The intracellular and tumor-specific nature of GdL3a and GdL3b were confirmed by magnetic resonance images of the cytosols and nuclei of various cell lines. The two complexes displayed antitumor activities with varying degrees of growth-inhibition and total-growth-inhibition values depending on the types of tumor cells. They caused morphological changes in tumor cell lines at much lower concentrations of gadolinium ([Gd] ≥ 50 μM) than their predecessors, DO3A-(p-aniline benzothiazole) conjugates (H3L1), and its GdIII complex (GdL1) required concentrations that were almost four times as high ([Gd] ≥ 200 μM). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Bae M.J.,Kyungpook National University | Lee Y.M.,Kyungpook National University | Kim Y.H.,Cheil Eye Research Institute | Han H.S.,Kyungpook National University | Lee H.J.,Seoul National University
Current Neurovascular Research | Year: 2015

The central nervous system is protected by the blood-brain barrier (BBB). The tight junction (TJ) proteins claudin-5 and zonula occludens-1 (ZO-1) as well as the cytoskeletal component F-actin play key roles in maintaining homeostasis of the BBB. Increases in BBB permeability may be beneficial for the delivery of pharmacological substances into the brain. Therefore, here, we assessed the use of ultrasound to induce transient enhancement of BBB permeability. We used fluorescein isothiocyanate (FITC)-dextran 40 to detect changes in the membrane permeability of bEnd.3 cells during ultrasound treatment. Ultrasound increased FITC-dextran 40 uptake into bEnd.3 cells for 2-6 h after treatment; however, normal levels returned after 24 h. An insignificant increase in lactate dehydrogenase (LDH) leakage also occurred 3 and 6 h after ultrasound treatment, whereas at 24 h, LDH leakage was indistinguishable between the control and treatment groups. Expression of claudin-5, ZO-1, and F-actin at the messenger RNA (mRNA) and protein levels was assessed with real-time polymerase chain reaction and western blotting. Ultrasound induced a transient decrease in claudin-5 mRNA and protein expression within 2 h of treatment; however, no significant changes in ZO-1 and F-actin expression were observed. Claudin-5, ZO-1, and F-actin immunofluorescence demonstrated that the cellular structures incorporating these proteins were transiently impaired by ultrasound. In conclusion, our ultrasound technique can temporarily increase BBB permeability without cytotoxicity to exposed cells, and the method can be exploited in the delivery of drugs to the brain with minimal damage. © 2015 Bentham Science Publishers. Source

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