title: Efficient lung orthotopic tumor-growth suppression of oncolytic adenovirus complexed with RGD-targeted bioreducible polymer.
abstract: Oncolytic adenoviruses (Ad) have been developed for the eradication of tumors. Although they hold much promise as a cancer therapy, they have a short blood circulation time and high liver toxicity. An effective strategy to overcome these problems has been complexing Ad with shielding materials. However, the therapeutic efficacy of the Ad complexes has also been an issue because passive accumulation does not allow for sufficient delivery of Ad to the cancer cells. To enhance the therapeutic efficacy of the polymer-coated Ads, the attachment of a targeting moiety to polymer-coated Ad vectors is inescapable. Our lab has previously reported the potential use of Arg-Gly-Asp (RGD)-targeted bioreducible polymers with a polyethylene glycol (PEG) linker for delivering oncolytic Ads. We have shown the enhanced in vitro transduction efficiency and increased cancer-killing effect with producing progeny oncolytic Ad particles. In addition, we have shown significant tumor-growth inhibition of the polymer-shielded Ad in an in vivo lung orthotopic tumor model. The shielding effect of the Ad surface with the polymers allowed evasion of host immune responses and reduction of liver toxicity. This data demonstrates that the RGD-conjugated bioreducible polymer for delivering the oncolytic Ad vectors could be utilized for cancer therapy via systemic administration.
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Samyang Biopharmaceuticals Corporation, Daejeon, South Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Nam
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea.
authors.forename: C-O
authors.initials: CO
authors.lastname: Yun
authors.affiliation: 1] Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA [2] Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000256:Adenoviridae / Q000737:chemistry; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000293:injuries / Q000821:virology; D008175:Lung Neoplasms / Q000628:therapy*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000737:chemistry; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D009842:Oligopeptides; D011108:Polymers; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid