Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 윤채옥 | - |
dc.date.accessioned | 2016-05-27T07:25:07Z | - |
dc.date.available | 2016-05-27T07:25:07Z | - |
dc.date.issued | 2015-01 | - |
dc.identifier.citation | BIOMACROMOLECULES, v. 16, NO 1, Page. 87-96 | en_US |
dc.identifier.issn | 1525-7797 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/21408 | - |
dc.identifier.uri | http://pubs.acs.org/doi/10.1021/bm501116x | - |
dc.description.abstract | Adenovirus (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.sponsorship | This 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.iso | en | en_US |
dc.publisher | AMER CHEMICAL SOC | en_US |
dc.title | Safety Profiles and Antitumor Efficacy of Oncolytic Adenovirus Coated with Bioreducible Polymer in the Treatment of a CAR Negative Tumor Model | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 16 | - |
dc.identifier.doi | 10.1021/bm501116x | - |
dc.relation.page | 87-96 | - |
dc.relation.journal | BIOMACROMOLECULES | - |
dc.contributor.googleauthor | Jung, Soo-Jung | - |
dc.contributor.googleauthor | Kasala, Dayananda | - |
dc.contributor.googleauthor | Choi, Joung-Woo | - |
dc.contributor.googleauthor | Lee, Soo-Hwan | - |
dc.contributor.googleauthor | Hwang, June Kyu | - |
dc.contributor.googleauthor | Kim, Sung Wan | - |
dc.contributor.googleauthor | Yun, Chae-Ok | - |
dc.relation.code | 2015001610 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF ENGINEERING[S] | - |
dc.sector.department | DEPARTMENT OF BIOENGINEERING | - |
dc.identifier.pid | chaeok | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.