Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model

Lee, Jangwook,Cha, Min-Ji,Lim, Kwang Suk,Kim, Jang-Kyung,Lee, Sang-Kyung,Kim, Yong-Hee,Hwang, Ki-Chul,Lee, Kuen Yong Informa UK Ltd. 2013 Journal of drug targeting Vol.21 No.9

<P>Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactic-<I>co</I>-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks <I>in vitro</I>. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated <I>in vivo</I>. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.</P>

Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarction

Lee, Jangwook,Tan, Cheau Yih,Lee, Sang-Kyung,Kim, Yong-Hee,Lee, Kuen Yong Elsevier 2009 Journal of controlled release Vol.137 No.3

<P><B>Abstract</B></P><P>Myocardial infarction causes a high rate of morbidity and mortality worldwide, and heat shock proteins as molecular chaperones have been attractive targets for protecting cardiomyoblasts under environmental stimuli. In this study, in order to enhance the penetration of heat shock protein 27 (HSP27) across cell membranes, we fused HSP27 with transcriptional activator (TAT) derived from human immunodeficiency virus (HIV) as a protein transduction domain (PTD). We loaded the fusion protein (TAT-HSP27) into microsphere/hydrogel combination delivery systems to control the release behavior for prolonged time periods. We found that the release behavior of TAT-HSP27 was able to be controlled by varying the ratio of PLGA microspheres and alginate hydrogels. Indeed, the released fusion protein maintained its bioactivity and could recover the proliferation of cardiomyoblasts cultured under hypoxic conditions. This approach to controlling the release behavior of TAT-HSP27 using microsphere/hydrogel combination delivery systems may be useful for treating myocardial infarction in a minimally invasive manner.</P> <P><B>Graphical abstract</B></P><P>The release behavior of TAT-HSP27 from microsphere/hydrogel combination systems was controlled over time, and the released protein was useful to recover the proliferation of cardiomyoblasts under hypoxic conditions.<ce:figure></ce:figure></P>

Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry

Lee, Si Yeon,Lee, Sangmin,Lee, Jangwook,Yhee, Ji Young,Yoon, Hwa In,Park, Soon-Jung,Koo, Heebeom,Moon, Sung-Hwan,Lee, Hyukjin,Cho, Yong Woo,Kang, Sun Woong,Lee, Sang-Yup,Kim, Kwangmeyung Elsevier 2016 Biochemical and biophysical research communication Vol.479 No.4

<P><B>Abstract</B></P> <P>Labeling of stem cells aims to distinguish transplanted cells from host cells, understand <I>in vivo</I> fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the <I>in vivo</I> evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated <I>N</I>-azidoacetyl-<SMALL>D</SMALL>-mannosamine (Ac<SUB>4</SUB>ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated <I>in vitro</I>. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track <I>in vivo</I> fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new method was proposed for labeling and tracking of stem cells. </LI> <LI> This method enables safe and long-term monitoring of stem cells <I>in vivo</I>. </LI> <LI> We observed the migration of the stem cells toward the ischemic lesion. </LI> </UL> </P>

T Cell-Specific siRNA Delivery Using Antibody-Conjugated Chitosan Nanoparticles

Lee, Jangwook,Yun, Kyoung-Soo,Choi, Chang Seon,Shin, Seung-Hwa,Ban, Hong-Seok,Rhim, Taiyoun,Lee, Sang Kyung,Lee, Kuen Yong American Chemical Society 2012 Bioconjugate chemistry Vol.23 No.6

<P>The intracellular delivery of small interfering RNA (siRNA) plays a key role in RNA interference (RNAi) and provides an emerging technique to treat various diseases, including infectious diseases. Chitosan has frequently been used in gene delivery applications, including siRNA delivery. However, studies regarding the modification of chitosan with antibodies specifically targeting T cells are lacking. We hypothesized that chitosan nanoparticles modified with T cell-specific antibodies would be useful for delivering siRNA to T cells. CD7-specific single-chain antibody (scFvCD7) was chemically conjugated to chitosan by carbodiimide chemistry, and nanoparticles were prepared by a complex coacervation method in the presence of siRNA. The mean diameter and zeta potential of the scFvCD7-chitosan/siRNA nanoparticles were approximately 320 nm and +17 mV, respectively, and were not significantly influenced by the coupling of antibody to chitosan. The cellular association of antibody-conjugated nanoparticles to CD4+ T cell lines as well as gene silencing efficiency in the cells was significantly improved compared to nonmodified chitosan nanoparticles. This approach to introducing T cell-specific antibody to chitosan nanoparticles may find useful applications for the treatment of various infectious diseases.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2012/bcches.2012.23.issue-6/bc2006219/production/images/medium/bc-2011-006219_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc2006219'>ACS Electronic Supporting Info</A></P>

Facile control of porous structures of polymer microspheres using an osmotic agent for pulmonary delivery

Lee, Jangwook,Oh, Yu Jin,Lee, Sang Kyung,Lee, Kuen Yong Elsevier 2010 Journal of controlled release Vol.146 No.1

<P><B>Abstract</B></P><P>It has been challenging to prepare polymeric microspheres with controlled porous structures for many biomedical applications, particularly for pulmonary drug delivery. Here, we report the use of bovine serum albumin (BSA) as an osmotic agent in order to control the porous structure of poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactide-co-glycolide) (PLGA) microspheres prepared by a double emulsion method. BSA was useful to induce osmosis between internal and external water phases during the double emulsion process, resulting in the fabrication of microspheres with controllable, uniform porous structures. The pore size of PLGA microspheres was controlled independently from the particle size by this approach. The use of BSA as an osmotic agent reduced the initial burst of model proteins (e.g., insulin and VEGF) entrapped in the porous microspheres, and the sustained release of VEGF was achieved for two weeks <I>in vitro</I>. This approach to controlling porous structures of polymer microspheres could be useful to develop novel pulmonary drug delivery systems.</P> <P><B>Graphical abstract</B></P><P>Polymer microspheres with uniform porous structures were prepared by the use of an osmotic agent, which can control the particle size and pore size independently.<ce:figure></ce:figure></P>

Injectable Microsphere/Hydrogel Combination Systems for Localized Protein Delivery

Lee, Jangwook,Lee, Kuen Yong WILEY-VCH Verlag 2009 Macromolecular bioscience Vol.9 No.7

<P>Injectable delivery systems for therapeutic proteins (e.g., hydrogels and microspheres) have attracted wide attention. Hydrogels, however, may release their hydrophilic contents too rapidly in a large initial burst, and phagocytes may clear microspheres within a relatively short time period after administration. We hypothesized that microsphere/hydrogel combination systems could achieve a controlled and sustained release of proteins as an injectable delivery system. To test this hypothesis, we prepared PLGA microspheres containing a model protein and mixed these with alginate gels. The mixing ratio of the components was the primary controlling parameter of the protein release. This approach could be useful for development of injectable and localized drug delivery systems.</P><P> <img src='wiley_img/16165187-2009-9-7-MABI200800317-gra001.gif' alt='wiley_img/16165187-2009-9-7-MABI200800317-gra001'> </P> <B>Graphic Abstract</B> <P>We demonstrate that combination systems composed of poly[(D,L-lactide)-co- glycolide] microspheres and alginate hydrogels can achieve a controlled and sustained release of model proteins as an injectable delivery system. The relative proportion of each component is found to be the major parameter for control of the protein release. This approach might be useful for design and development of injectable delivery systems for various biomedical applications. <img src='wiley_img/16165187-2009-9-7-MABI200800317-content.gif' alt='wiley_img/16165187-2009-9-7-MABI200800317-content'> </P>

Local and Sustained Vascular Endothelial Growth Factor Delivery for Angiogenesis Using an Injectable System

Lee, Jangwook,Lee, Kuen Yong Springer-Verlag 2009 Pharmaceutical research Vol.26 No.7

Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

Lee, Jangwook,Bhang, Suk Ho,Park, Honghyun,Kim, Byung-Soo,Lee, Kuen Yong Springer-Verlag 2010 Pharmaceutical research Vol.27 No.5

S-200 A mediastinal mass presented as tachy-bradycardia syndrome

( Jangwook Lee ),( Young-Kwon Kim ),( Jinho Choi ),( Eo Jin Kim ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

A 46-year old man was admitted to the cardiovascular department because of the sudden onset of chest pain and loss of consciousness at resting state. The first episode of symptomatic paroxysmal atrial fibrillation (AF) was diagnosed 5 days ago at local clinic with electrocardiogram. At admission, laboratory results were normal and initial electrocardiogram showed AF with slow ventricular rate with low blood pressure, so we administered normal saline and dopamine. We did not administer antiarrhythmic agent due to risk of embolism. Chest X-ray showed suggestive of subcarinal mass and in echocardiography, ejection fraction was 54% and regional wall motion abnormality was not detected but loss of A-wave and compression of left atrium by extracardiac mass were detected. And we inserted temporary pacemaker due to possibility of sudden symptomatic bradycardia event. Chest computed tomography and mediastinal and chest wall magnetic resonance imaging were also performed. 7.7 cm sized well defined bronchogenic cyst without solid portion was in subcarinal area and also compressed pulmonary artery and left atrium. (Figure 1.) The cyst was completely excised using video-assisted thoracoscopic surgery. Histopathologic examination revealed a benign bronchogenic cyst. (Figure 2.) He converted to sinus rhythm on the postoperative day and discharged from hospital. To our knowledge, this is the first case of a patient with tachy-bradycardia syndrome caused by a mediastinal mass impinging on the left atrium in South Korea.

Superior electrochemical performance of N-doped nanocrystalline FeF₃/C with a single-step solid-state process

Lee, Jangwook,Kang, Byoungwoo The Royal Society of Chemistry 2016 Chemical communications Vol.52 No.81

<P>FeF3 is a promising cathodematerial for lithium ion batteries but its poor electronic conductivity makes it non-practical. Here, we significantly improve the electrochemical activity of FeF3 by reducing the strong ionic character of Fe-F with the replacement of some F with N atoms. N-doped nanocrystalline FeF3/C achieves the best electrochemical performance among FeF3 compounds reported to date: similar to 95 mA h g(-1) at 21.1C discharge rate for 250 cycles. The results illustrate that the poor electronic conductivity of metal fluorides can be controlled by doping and this enables FeF3 or metal fluorides to be practically utilized in possible applications including energy conversion and storage.</P>