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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.<\/jats:p>","DOI":"10.1021\/bm501116x","type":"journal-article","created":{"date-parts":[[2014,11,15]],"date-time":"2014-11-15T16:09:48Z","timestamp":1416067788000},"page":"87-96","source":"Crossref","is-referenced-by-count":32,"title":["Safety Profiles and Antitumor Efficacy of Oncolytic\nAdenovirus Coated with Bioreducible Polymer in the Treatment of a\nCAR Negative Tumor Model"],"prefix":"10.1021","volume":"16","author":[{"given":"Soo-Jung","family":"Jung","sequence":"first","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayananda","family":"Kasala","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joung-Woo","family":"Choi","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June Kyu","family":"Hwang","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Wan","family":"Kim","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]},{"name":"University of Utah , , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Ok","family":"Yun","sequence":"additional","affiliation":[{"name":"Hanyang University , , 222 Wangsimni-ro , ,","place":["Seongdong-gu, Seoul, Korea, 133-791"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,11,15]]},"reference":[{"key":"2026090301544136000_cit1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2003.09.013","volume":"94","author":"El-Aneed","year":"2004","journal-title":"J. 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