Linearized oncolytic adenoviral plasmid DNA delivered by bioreducible polymers

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• 作者：Jaesung Kim^a ; Pyung-Hwan Kim^a ; Hye Yeong Nam^a ; Jung-Sun Lee^b ; ^c ; Chae-Ok Yun^c ; ^{chaeok@hanyang.ac.kr} ; Sung Wan Kim^a ; ^c ; ^{SW.Kim@pharm.utah.edu}
• 关键词：Oncolytic adenovirus ; Adenoviral replication ; Bioreducible polymer ; Cancer gene therapy
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：28 March, 2012
• 卷：158
• 期：3
• 页码：451-460
• 文件大小：1249 K

摘要

As an effort to overcome limits of adenovirus (Ad) as a systemic delivery vector for cancer therapy, we developed a novel system using oncolytic Ad plasmid DNA with two bioreducible polymers: arginine-grafted bioreducible poly(disulfide amine)polymer (ABP) and PEG5k-conjugated ABP (ABP5k) in expectation of oncolytic effect caused by progeny viral production followed by replication. The linearized Ad DNAs for active viral replication polyplexed with each polymer were able to replicate only in human cancer cells and produce progeny viruses. The non-immunogenic polymers delivering the DNAs markedly elicited to evade the innate and adaptive immune response. The biodistribution ratio of the polyplexes administered systemically was approximately 99%decreased in liver when compared with naked Ad. Moreover, tumor-to-liver ratio of the Ad DNA delivered by ABP or ABP5k was significantly elevated at 229- or 419-fold greater than that of naked Ad, respectively. The ABP5k improved the chance of the DNA to localize within tumor versus liver with 1.8-fold increased ratio. In conclusion, the innovative and simple system for delivering oncolytic Ad plasmid DNA with the bioreducible polymers, skipping time-consuming steps such as generation and characterization of oncolytic Ad vectors, can be utilized as an alternative approach for cancer therapy.