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Therapeutic efficacy of a systemically delivered oncolytic adenovirus – Biodegradable polymer complex

Paper ID Volume ID Publish Year Pages File Format Full-Text
6630 508 2013 10 PDF Available
Title
Therapeutic efficacy of a systemically delivered oncolytic adenovirus – Biodegradable polymer complex
Abstract

Despite great efforts to develop a more effective oncolytic adenovirus (Ad) for eradicating tumors, in vivo application via systemic administration is strictly limited to local injection due to host immune responses by Ad surface proteins and liver accumulation by the inherent nature of the Ad. In the last decade, numerous techniques using synthetic polymers have widely emerged to shield the exterior of therapeutic Ad vectors for systemic delivery. We developed a cationic polymer linked with polyethylene glycol for systemically delivering oncolytic Ad. The increased transduction efficiency and oncolytic effect of the Ad vectors physically coated with the polymer were evaluated, showing the optimal size (130 nm) of the Ad/polymer complex for systemic administration and prolonged stability of the Ad/polymer complex. Marked tumor growth suppression of the oncolytic Ad delivered by the polymer through systemic injection was observed in HT1080 and A549 xenograft models. The masking effect of the Ad surface by the polymer elicited evasion of innate adaptive immune responses and the tumor-to-liver ratio of the complex was significantly elevated 1229-fold greater than that of a naked Ad. These results demonstrate that the potential system of oncolytic Ad complexed with the biodegradable polymer may be useful for developing therapeutic vector systems via systemic delivery.

Keywords
Oncolytic adenovirus; Biodegradable polymer; Anti-tumoral effect; Cancer gene therapy
First Page Preview
Therapeutic efficacy of a systemically delivered oncolytic adenovirus – Biodegradable polymer complex
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 19, June 2013, Pages 4622–4631
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering