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        Self-assembled hyaluronic acid nanoparticles as a potential drug carrier for cancer therapy: synthesis, characterization, and <i>in vivo</i> biodistribution

        Choi, Ki Young,Min, Kyung Hyun,Na, Jin Hee,Choi, Kuiwon,Kim, Kwangmeyung,Park, Jae Hyung,Kwon, Ick Chan,Jeong, Seo Young Royal Society of Chemistry 2009 Journal of materials chemistry Vol.19 No.24

        <P>To develop a nano-sized drug delivery system for cancer therapy, amphiphilic hyaluronic acid conjugates were synthesized by chemical conjugation of hydrophobic 5β-cholanic acid to the backbone of hyaluronic acid (HA). The HA conjugates could form nano-sized self-aggregates under physiological conditions (PBS, pH = 7.4, 37 °C) <I>via</I> the hydrophobic interaction among 5β-cholanic acids. The HA nanoparticles were spherical in shape and their sizes were in the range of 350–400 nm, depending on the degree of substitution of 5β-cholanic acid. From a cellular experiment using Cy5.5-labeled HA nanoparticles, it was demonstrated that they are efficiently taken up by SCC7 cancer cells which over-express CD44, the receptor for HA. When the Cy5.5-labeled HA nanoparticles were systemically administrated into the tail vein of tumor-bearing mice, most of the nanoparticles were found in tumor and liver sites. In particular, the fluorescence intensity of nanoparticles at the tumor site was 4-fold higher than that of pure HA polymer, which was confirmed by a non-invasive near-infrared fluorescence imaging system. The high tumor targeting ability of HA nanoparticles might result from both their prolonged circulation in blood and high affinity to tumor cells. These results reveal the promising potential of HA nanoparticles as a stable and effective nano-sized drug delivery system for cancer treatment.</P> <P>Graphic Abstract</P><P>The HA conjugates could form self-assembled nanoparticles in an aqueous condition. The HA nanoparticles are efficiently taken up by the SCC7 cancer cells <I>in vitro</I> and accumulated in tumor site <I>in vivo</I>. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b900456d'> </P>

      • Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy

        Choi, Ki Young,Yoon, Hong Yeol,Kim, Jong-Ho,Bae, Sang Mun,Park, Rang-Woon,Kang, Young Mo,Kim, In-San,Kwon, Ick Chan,Choi, Kuiwon,Jeong, Seo Young,Kim, Kwangmeyung,Park, Jae Hyung American Chemical Society 2011 ACS NANO Vol.5 No.11

        <P>Tumor targetability and site-specific drug release of therapeutic nanoparticles are key factors for effective cancer therapy. In this study, poly(ethylene glycol) (PEG)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) were investigated as carriers for anticancer drugs including doxorubicin and camptothecin (CPT). P-HA-NPs were internalized into cancer cells (SCC7 and MDA-MB-231) <I>via</I> receptor-mediated endocytosis, but were rarely taken up by normal fibroblasts (NIH-3T3). During <I>in vitro</I> drug release tests, P-HA-NPs rapidly released drugs when incubated with cancer cells, extracts of tumor tissues, or the enzyme Hyal-1, which is abundant in the intracellular compartments of cancer cells. CPT-loaded P-HA-NPs (CPT-P-HA-NPs) showed dose-dependent cytotoxicity to cancer cells (MDA-MB-231, SCC7, and HCT 116) and significantly lower cytotoxicity against normal fibroblasts (NIH-3T3) than free CPT. Unexpectedly, high concentrations of CPT-P-HA-NPs demonstrated greater cytotoxicity to cancer cells than free CPT. An <I>in vivo</I> biodistribution study indicated that P-HA-NPs selectively accumulated into tumor sites after systemic administration into tumor-bearing mice, primarily due to prolonged circulation in the blood and binding to a receptor (CD44) that was overexpressed on the cancer cells. In addition, when CPT-P-HA-NPs were systemically administrated into tumor-bearing mice, we saw no significant increases in tumor size for at least 35 days, implying high antitumor activity. Overall, P-HA-NPs showed promising potential as a drug carrier for cancer therapy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2011/ancac3.2011.5.issue-11/nn202070n/production/images/medium/nn-2011-02070n_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn202070n'>ACS Electronic Supporting Info</A></P>

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      • Detection of Active Matrix Metalloproteinase-3 in Serum and Fibroblast-Like Synoviocytes of Collagen-Induced Arthritis Mice

        Lee, Aeju,Choi, Sung-Jae,Park, Kyeongsoon,Park, Jong Woong,Kim, Kwangmeyung,Choi, Kuiwon,Yoon, Soo-Young,Youn, Inchan American Chemical Society 2013 Bioconjugate chemistry Vol.24 No.6

        <P>The activity of rheumatoid arthritis (RA) correlates with the expression of proteases. Among several proteases, matrix metalloproteinase-3 (MMP-3) is one of the biological markers used to diagnose RA. The active form of MMP-3 is a key enzyme involved in RA-associated destruction of cartilage and bone. Thus, detection of active MMP-3 in serum or <I>in vivo</I> is very important for early diagnosis of RA. In this study, a soluble MMP-3 probe was prepared to monitor RA progression by detecting expression of active MMP-3 in collagen-induced arthritis (CIA) mice <I>in vivo</I> in both serum and fibroblast-like synoviocytes (FLSs). The MMP-3 probe exhibited strong sensitivity to MMP-3 and moderate sensitivity to MMP-7 at nanomolecular concentrations, but was not sensitive to other MMPs such as MMP-2, MMP-9, and MMP-13. In an optical imaging study, the MMP-3 probe produced early and strong NIR fluorescence signals prior to observation of erythema and swelling in CIA mice. The MMP-3 probe was able to rapidly and selectively detect and monitor active MMP-3 in diluted serum from CIA mice. Furthermore, histological data demonstrated that activated FLSs in arthritic knee joints expressed active MMP-3. Together, our results demonstrated that the MMP-3 probe may be useful for detecting active MMP-3 for diagnosis of RA. More importantly, the MMP-3 probe was able to detect active MMP-3 in diluted serum with high sensitivity. Therefore, the MMP-3 probe developed in this study may be a very promising probe, useful as a biomarker for early detection and diagnosis of RA.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2013/bcches.2013.24.issue-6/bc4001273/production/images/medium/bc-2013-001273_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc4001273'>ACS Electronic Supporting Info</A></P>

      • KCI등재

        Automated Feature - Based Registration for Reverse Engineering of Human Models

        Yongtae Jun,Kuiwon Choi 대한기계학회 2005 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.19 No.12

        In order to reconstruct a full 3D human model in reverse engineering (RE), a 3D scanner needs to be placed arbitrarily around the target model to capture all part of the scanned surface. Then, acquired multiple scans must be registered and merged since each scanned data set taken from different position is just given in its own local co-ordinate system. The goal of the registration is to create a single model by aligning all individual scans. It usually consists of two sub-steps : rough and fine registration. The fine registration process can only be performed after an initial position is approximated through the rough registration. Hence an automated rough registration process is crucial to realize a completely automatic RE system. In this paper an automated rough registration method for aligning multiple scans of complex human face is presented. The proposed method automatically aligns the meshes of different scans with the information of features that are extracted from the estimated principal curvatures of triangular meshes of the human face. Then the roughly aligned scanned data sets are further precisely enhanced with a fine registration step with the recently popular Iterative Closest Point (ICP) algorithm. Some typical examples are presented and discussed to validate the proposed system.

      • SCIESCOPUS

        Prediction of Antiarthritic Drug Efficacies by Monitoring Active Matrix Metalloproteinase-3 (MMP-3) Levels in Collagen-Induced Arthritic Mice Using the MMP-3 Probe

        Lee, Aeju,Park, Kyeongsoon,Choi, Sung-Jae,Seo, Dong-Hyun,Kim, Kwangmeyung,Kim, Han Sung,Choi, Kuiwon,Kwon, Ick Chan,Yoon, Soo-Young,Youn, Inchan American Chemical Society 2014 MOLECULAR PHARMACEUTICS Vol.11 No.5

        <P>Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2014/mpohbp.2014.11.issue-5/mp400622q/production/images/medium/mp-2013-00622q_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/mp400622q'>ACS Electronic Supporting Info</A></P>

      • Hydrotropic magnetic micelles for combined magnetic resonance imaging and cancer therapy

        Yoon, Hong Yeol,Saravanakumar, Gurusamy,Heo, Roun,Choi, Seung Hong,Song, In Chan,Han, Moon Hee,Kim, Kwangmeyung,Park, Jae Hyung,Choi, Kuiwon,Kwon, Ick Chan,Park, Kinam Elsevier 2012 Journal of controlled release Vol.160 No.3

        <P><B>Abstract</B></P><P>Polymeric nanoparticles, capable of encapsulating imaging agents and therapeutic drugs, have significant advantages for simultaneous diagnosis and therapy. Nonetheless, improvements in the loading contents of the active agents are needed to achieve enhanced imaging and effective therapeutic outcomes. Aiming to make these improvements, a hydrotropic micelle (HM) was explored to encapsulate superparamagnetic iron oxide nanoparticles (SPIONs) as the magnetic resonance (MR) imaging agent and paclitaxel (PTX) as the hydrophobic anticancer drug. Owing to its hydrotropic inner core with hydrophobic nature, HM could effectively encapsulate both of PTX and SPION via the simple dialysis method. The hydrodynamic size of HM increased from 68 to 178nm after physical encapsulation of SPION and PTX. Transmission electron microscopy analysis of HM bearing SPION and PTX (HM-SPION-PTX) revealed a spherical morphology with SPION clusters in the micelle cores. The micelles released PTX in a sustained manner. The bare HM and HM-SPION showed no toxicity to SCC7 cells, whereas HM-PTX and HM-SPION-PTX showed dose-dependent cytotoxicity that was lower than free PTX. HM-SPION-PTX exhibited 8.1-fold higher <I>T</I><SUB>2</SUB> relaxivity than HM-SPION, implying potential of HM-SPION-PTX as the contrast agent for MR imaging. When systemically administered to tumor-bearing mice, HM-SPION-PTX was effectively accumulated at the tumor site, allowing its detection using MR imaging and effective therapy. Overall, these results suggested that HM-SPION-PTX is a promising candidate for combined diagnosis and treatment of cancer.</P> <P><B>Graphical abstract</B></P><P>Hydrotropic micelles bearing the MR contrast agents and paclitaxel allow for detection and effective therapy of tumor.<ce:figure id='f0005'></ce:figure></P>

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