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dc.contributor.author윤채옥-
dc.date.accessioned2016-05-27T07:25:07Z-
dc.date.available2016-05-27T07:25:07Z-
dc.date.issued2015-01-
dc.identifier.citationBIOMACROMOLECULES, v. 16, NO 1, Page. 87-96en_US
dc.identifier.issn1525-7797-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/21408-
dc.identifier.urihttp://pubs.acs.org/doi/10.1021/bm501116x-
dc.description.abstractAdenovirus (Ad) vectors show promise as cancer gene therapy delivery vehicles, but immunogenic safety concerns and coxsackie and adenovirus receptor (CAR)-dependency have limited their use. Alternately, biocompatible and bioreducible nonviral vectors, including arginine-grafted cationic polymers, have been shown to deliver nucleic acids through a cell penetration peptide (CPP) and protein transduction domain (PTD) effect. We utilized the advantages of both viral and nonviral vectors to develop a hybrid gene delivery vehicle by coating Ad with mPEG-PEI-g-Arg-S-S-Arg-g-PEI-mPEG (Ad/PPSA). Characterization of Ad/PPSA particle size and zeta potential showed an overall size and cationic charge increase in a polymer concentration-dependent manner. Ad/PPSA also showed a marked transduction efficiency increase in both CAR-negative and -positive cells compared to naked Ad. Competition assays demonstrated that Ad/PPSA produced higher transgene expression levels than naked Ad and achieved CAR-independent transduction. Oncolytic Ad (DWP418)/PPSA was able to overcome the nonspecificity of polymer-only therapies by demonstrating cancer-specific killing effects. Furthermore, the DWP418/PPSA nanocomplex elicited a 2.24-fold greater antitumor efficacy than naked Ad in vivo. This was supported by immunohistochemical confirmation of Ad E1As accumulation in MCF7 xenografted tumors. Lastly, intravenous injection of DWP418/PPSA elicited less innate immune response compared to naked Ad, evaluated by interleukin-6 cytokine release into the serum. The increased antitumor effect and improved vector targeting to both CAR-negative and -positive cells make DWP418/PPSA a promising tool for cancer gene therapy.en_US
dc.description.sponsorshipThis work was supported by grants from the Ministry of Trade, Industry & Energy (10030051, Dr. C.-O. Yun), the National Research Foundation of Korea (2010-0029220, 2013K1A1A2A02050188, 2013M3A9D3045879, Dr. C.-O. Yun), the Korea Food and Drug Administration (KFDA-13172-306, Dr. C.-O. Yun), Basic Research Programs by National Research Foundation of Korea (2013R1A1A2012483, Dr. D. Kasala) and the National Institutes of Health, USA (CA 107070, Dr. S.-W. Kim).-
dc.language.isoenen_US
dc.publisherAMER CHEMICAL SOCen_US
dc.titleSafety Profiles and Antitumor Efficacy of Oncolytic Adenovirus Coated with Bioreducible Polymer in the Treatment of a CAR Negative Tumor Modelen_US
dc.typeArticleen_US
dc.relation.no1-
dc.relation.volume16-
dc.identifier.doi10.1021/bm501116x-
dc.relation.page87-96-
dc.relation.journalBIOMACROMOLECULES-
dc.contributor.googleauthorJung, Soo-Jung-
dc.contributor.googleauthorKasala, Dayananda-
dc.contributor.googleauthorChoi, Joung-Woo-
dc.contributor.googleauthorLee, Soo-Hwan-
dc.contributor.googleauthorHwang, June Kyu-
dc.contributor.googleauthorKim, Sung Wan-
dc.contributor.googleauthorYun, Chae-Ok-
dc.relation.code2015001610-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF ENGINEERING[S]-
dc.sector.departmentDEPARTMENT OF BIOENGINEERING-
dc.identifier.pidchaeok-
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COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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