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Tumor-specific delivery of therapeutic siRNAs by anti-EGFR immunonanoparticles
Kim, Jung Seok,Kim, Min Woo,Kang, Seong Jae,Jeong, Hwa Yeon,Park, Sang Il,Lee, Yeon Kyung,Kim, Hong Sung,Kim, Keun Sik,Park, Yong Serk Dove Medical Press 2018 International journal of nanomedicine Vol.13 No.-
<P><B>Background</B></P><P>Efficient target-specific siRNA delivery has always been a primary concern in the field of siRNA clinical application.</P><P><B>Purpose</B></P><P>In this study, four different types of anti-epidermal growth factor receptor (EGFR) antibody-conjugated immunonanoparticles were prepared and tested for cancer cell-targeted therapeutic siRNA delivery.</P><P><B>Materials and methods</B></P><P>The prepared nanoparticles encapsulating siRNAs were character-ized by gel retardation and particle analysis using a Zetasizer. In vitro transfection and reduction of target genes, vimentin and JAK3, were determined using quantitative reverse transcription polymerase chain reaction. In vivo tumor targeting and antitumoral efficacies of the nanoparticles were evaluated in mice carrying tumors.</P><P><B>Results</B></P><P>Among these immunonanoparticles, anti-EGFR immunolipoplexes and immunoviroplexes exhibited remarkable cell binding and siRNA delivery to EGFR-expressing tumor cells compared to immunoliposomes and immunovirosomes. Especially, the anti-EGFR immunoviroplexes exhibited the most efficient siRNA transfection to target tumor cells. Therefore, antitumoral vimentin and Janus kinase-3 siRNAs were loaded in the anti-EGFR immunolipoplexes and immunoviroplexes, which were tested in mice carrying SK-OV-3 tumor xenografts. In fact, the therapeutic siRNAs were efficiently delivered to the tumor tissues by both delivery vehicles, resulting in significant inhibition of tumor growth. Moreover, administration of doxorubicin in combination with anti-EGFR immunoviroplexes resulted in remarkable and synergistic tumor growth inhibition.</P><P><B>Conclusion</B></P><P>This study provides experimental proof that cancer cell-targeted immunoviroplexes are an efficient siRNA delivery system for cancer therapy. Moreover, this study also suggests that a combination of conventional chemotherapy and tumor-directed anticancer siRNA therapy would be a better modality for cancer treatment.</P>
Kim, Keun-Sik,Park, Yong-Serk,Hong, Hyo-Jeong,Kim, Kwang-Pyo,Lee, Kwang-Hyun,Kim, Dong-Eun Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.2
Cationic immunoliposomes were prepared by conjugation of Fab' fragments of the recombinant humanized monoclonal antibody (HuCC49) against tumor-associated glycoprotein (TAG)-72 to sterically unilamella liposomes. The cationic immunoliposomes are composed of cationic lipid (O,O'-dimyristyl-N-lysyl aspartate, DMKD), cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethyleneglycol)$_{2000}$] (DPPE-PEG-maleimide) with a molar ratio of 0.5:0.47:0.03. Plasmid DNA was effectively condensed by addition of transferrin (Tf) during the formation of anti-TAG-72 PEG-immunolipoplexes (PILPs). These anti-TAG-72 PILPs were able to adhere to the surface of TAG-72-overexepressing LS174T human colon cancer cells more effectively than conventional liposomes, thereby facilitating gene delivery in vitro. Furthermore, intravenous administration of the anti-TAG-72 PILPs into the tumor-carrying mice exhibited efficient localization of the reporter gene in the tumor tissues.
Kim, Hyoseon,Lee, Kwang Hyun,Kim, Kyung Bo,Park, Yong Serk,Kim, Keun-Sik,Kim, Dong-Eun Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.3
Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.
모바일용 디지털 오디오 스피커를 위한 고효율 드라이버 설계
김용석(Yong-Serk Kim),임민중(Min-Joon Rim) 대한전기학회 2011 전기학회논문지 P Vol.60 No.1
In this paper, we designed Interpolation FIR(Finite Impulse Response) filter and L-bit SDM(Sigma-Delta Modulator) for small digital audio speaker, which has low power consumption and high output characteristics. In order to achieve high linearity and low distortion performance of the systems, we adopt Type Ⅰ Chevychev FIR filter which has equiripple characteristics in the pass band and proposed high efficient FIR filter structure. SDM is the most efficient modulation technique among the noise shaping techniques. In this paper, we implemented SDM using CIFB(Cascade of Intergrators, Feed-Back) which is generally used in DAC of small digital audio speakers. The proposed SDM structure can achieve high SNR, high-efficiency characteristics and low power consumption in mobile devices. Also considering manufacture of SoC(System on Chip), we performed simulation with Matlab and Verilog HDL to obtain optimal number of operational bits and verified a good experimental results.
CO2레이저와 5% Imiquimod 크림 병합요법으로 치료한 기저세포암
권용현 ( Yong Hyun Kwon ),남재희 ( Jae Hui Nam ),김태환 ( Tae Hwan Kim ),이가영 ( Ga Young Lee ),김원석 ( Won Serk Kim ),김계정 ( Kea Jeung Kim ) 대한피부과학회 2007 대한피부과학회지 Vol.45 No.11
Basal cell carcinoma is the most common skin cancer and surgical treatments like Mohs surgery have been accepted as ideal for it. Although surgical treatments are very effective, non-invasive treatments such as electrocauterization, cryosurgery, CO2 laser and topical 5-fluorouracil cream have been tried because patients need more simple procedures and better cosmetic results. Imiquimod is a Toll-like receptor 7 agonist and which acts as an immune response modifier by inducing several cytokines including interferon. Previously, many reports showed the usefulness of 5% imiquimod cream in treating basal cell carcinoma. However, some local adverse effects, long treatment time and limitation of deep penetration are problems to be resolved. We tried 5% imiquimod cream application after the removal of a visible basal cell carcinoma using CO2 laser, which gave satisfactory results. (Korean J Dermatol 2007;45(11):1187∼1190)
Antiwrinkle effect of adipose-derived stem: Activation of dermal fibroblast by secretory factors
( Tae Hwan Kim ),( Young Jun Choi ),( Jae Hui Nam ),( Yong Hyun Kwon ),( Ga Young Lee ),( Soo Hong Park ),( Won Serk Kim ),( Kea Jeung Kim ),( So Hyun Park ),( Hyung Ki Kim ),( Jong Hyuk Sung ) 대한피부과학회 2008 초록집 Vol.46 No.20