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Che, Hui-Lian,Muthiah, Muthunarayanan,Ahn, Youngkeun,Son, Sejin,Kim, Won Jong,Seonwoo, Hoon,Chung, Jong Hoon,Cho, Chong-Su,Park, In-Kyu American Scientific Publishers 2011 Journal of Nanoscience and Nanotechnology Vol.11 No.8
<P>In this study, we present nanofiber-mediated gene delivery for myocardial infarction (MI). Branched polyethylenimine cross-linked via disulfide bonds (ssPEI) complexed with vascular endothelial growth factor (VEGF) were immobilized on electrospun polycaprolactone (PCL)/polyethylenimine (PEI) nanofibers for the local expression of VEGF angiogenic factor. We studied whether the production of VEGF from myoblast cells adhering on the nanofibers has therapeutic potential for MI. In this method, the non-specific adsorption of VEGF nanoparticles to the nanofibers occurred uniformly over all of the surface area of the nanofibers, resulting in increased transgene uptake and expression in a great number of cells. The amount of DNA required for transfection was also minimal compared to bolus delivery, because the adhered DNA was directly available in the cell microenvironment, which also helps in localized delivery. Reporter genes luciferase (Luc), red fluorescence protein (RFP), and therapeutic gene VEGF were tested to evaluate the transfection efficiency of ssPEI nanoparticles immobilized on the nanofiber surface. Our results demonstrated that the delivery of therapeutic genes from biodegradable nanoparticles immobilized on the nanofiber represented minimal cytotoxicity of H9C2 myoblasts than branched PEI 25 kDa did. According to Luc assay, fluorescence microscope analysis, and reverse transcription polymerase chain reaction (RT-PCR), this vector showed high transgene expression efficiency to the reporter gene and VEGF gene. The surface-mediated delivery of the DNA nanoparticles did not adversely affect cell growth, and facilitated the transgene expression inside the cells.</P>
Hui-Lian Che,In-Ho Bae,Kyung-Seob Lim,Saji Uthaman,In Taek Song,이해신,이두환,김원종,Young Keun Ahn,박인규,Myung Ho Jeong 대한심장학회 2016 Korean Circulation Journal Vol.46 No.1
Background and Objectives: MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. Materials and Methods: For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon- injured external iliac artery in a rabbit restenosis model. Results: Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri- stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in- stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. Conclusion: MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent.
Drug- and Gene-eluting Stents for Preventing Coronary Restenosis
Kamali Manickavasagam Lekshmi,Hui-Lian Che,조정수,박인규 전남대학교 의과학연구소 2017 전남의대학술지 Vol.53 No.1
Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions
Drug- and Gene-eluting Stents for Preventing Coronary Restenosis
Lekshmi, Kamali Manickavasagam,Che, Hui-Lian,Cho, Chong-Su,Park, In-Kyu Chonnam National University Medical School 2017 CMJ Vol.53 No.1
<P>Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions.</P>
이상준,박인규,Muthunarayanan Muthiah,이현진,이화정,문명주,Hui-Lian Che,허선우,이현철,정용연 한국고분자학회 2012 Macromolecular Research Vol.20 No.2
Superparamagnetic iron oxide nanoparticle (SPION)-based diagnostic properties with accompanying therapeutics such as drugs or genes have been explored for improvement of their therapeutic efficacy. Positively charged SPION-loaded polymersomes was prepared to deliver genes to the target sites; this process was concomitantly monitored by magnetic resonance imaging (MRI). The surface characteristics and morphology were respectively measured by dynamic light scattering and transmission electron microscopy. The complex between the polymer and the pDNA was confirmed by a gel retardation assay. The transfection efficiency and cytotoxicity in vitro were tested by treating of the CT-26 colon cancer cell line with luciferase-expressing plasmids/SPION complex. MRI was also used to check the detectability of SPION in vitro and in vivo. A SPION-loaded polymersome carrying genetic materials was delivered and then accumulated in the tumor site of the murine colon cancer xenograft model after intravenous injection, possibly through a passive targeting mechanism. The accumulation was monitored using clinical MRI. This result indicates that the SPION-loaded polymersome can be applied to MR imageguided gene therapy.
Zhou, Cui,Jiang, Song-Song,Wang, Cui-Yan,Li, Rong,Che, Hui-Lian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8
To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells.