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Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy

Gene Therapy volume 20, pages 880–892 (2013)Cite this article

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Abstract

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

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Acknowledgements

This research was supported by grants from the Ministry of Knowledge Economy (10030051, to C-OY), the Korea Science and Engineering Foundation (R15-2004-024-02001-0, 2009K001644, 2010-0029220, to C-OY), the Korea Food and Drug Administration (KFDA-10172-332, to C-OY), the Research Fund (WCU 200900000000024, S-WK) of the Ministry of Education, Science and Technology, Korea, and (CA 107070, S-WK) of the National Institutes of Health, USA.

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  1. J-W Choi and E Kang: These authors contributed equally to this study.

Authors and Affiliations

  1. Graduate Program for Nanomedical Science, Yonsei University, Seoul, Republic of Korea

    J-W Choi

  2. Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea

    E Kang, O-J Kwon, T J Yun, P-H Kim, S W Kim & C-O Yun

  3. Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Korea

    H-K Park & J H Kim

  4. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA

    S W Kim

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  1. J-W Choi
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Correspondence to J H Kim or C-O Yun.

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Choi, JW., Kang, E., Kwon, OJ. et al. Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy. Gene Ther 20, 880–892 (2013). https://doi.org/10.1038/gt.2013.10

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