In Vivo Therapeutic Efficacy of Oncolytic Adenovirus Delivered by New Biodegradable Polymers through Systemic Injection

초록

Despite all efforts to develop 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 inherent nature of Ad. In a recent decade, numerous techniques using synthetic polymers have widely emerged to shield the exterior of therapeutic Ad vectors for systemic delivery. We developed a novel cationic polymer linked with polyethylene glycol for delivering oncolytic Ad systemically. Increased transduction efficiency and oncolytic effect of Ad vectors physically coated with the polymer were evaluated, with showing optimal size (130 nm) of the Ad/polymer complex for systemic administration and prolonged stability of 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. Masking effect of the Ad surface by the polymer elicited evasion of innate & adaptive immune responses and tumor-to-liver ratio of the complex was significantly elevated at 1229-fold greater than that of naked Ad. These results demonstrate that the potential system of oncolytic Ad complexed with the biodegradable polymer might be useful for developing therapeutic vector systems via systemic delivery.