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dc.contributor.author윤채옥-
dc.date.accessioned2018-02-12T08:52:52Z-
dc.date.available2018-02-12T08:52:52Z-
dc.date.issued2011-10-
dc.identifier.citationIn Proceedings of the Fifthteenth International Symposium on Recent Advances in Drug Delivery Systems, Journal of Controlled Release, 155(2), 317-325en_US
dc.identifier.issn0168-3659-
dc.identifier.urihttp://www.sciencedirect.com/science/article/pii/S0168365911004020?via%3Dihub-
dc.description.sponsorshipModifying the viral genome to express potent and cancer-selective therapeutic genes has enhanced the role of adenoviruses (Ads) in cancer molecular therapeutics. However, the efficacy of Ad systemic delivery in vivo is limited by neutralizing antibodies, short blood circulation time, and high levels of nonspecific liver uptake resulting in hepatotoxicity. We therefore investigated the systemic delivery of tumor necrosis factor-related apoptosis-inducing ligand-expressing oncolytic Ad genome DNA (pmT-d19/stTR) via lipid envelopment as an alternative approach for cancer virotherapy in an orthotopic lung cancer model. Cationic liposomes (DOTAP/DOPE) were complexed with pmT-d19/stTR to generate pmT-d19/stTR+DOTAP/DOPE with the average diameter of which was 143.3±5.7nm at the optimal DNA:lipid ratio (1:6). Systemic administration of pmT-d19/stTR+DOTAP/DOPE elicited highly effective antitumor responses in vivo, with tumor volumes decreasing 94.5%, 90.5%, and 92.4% compared to phosphate buffered saline-, naked Ad (mT-d19/stTR)-, or pmT-d19/stTR-treated groups, respectively. Additionally, innate immune responses and Ad-specific neutralizing antibodies were significantly decreased in pmT-d19/stTR+DOTAP/DOPE-treated mice compared to those in the mT-d19/stTR-treated group. The biodistribution profile analyzed by quantitative-PCR and immunohistochemical analysis demonstrated that viral replication occurred preferentially in tumor tissues. Moreover, the viral genome tumor-to-liver ratio was significantly elevated in pmT-d19/stTR+DOTAP/DOPE-treated mice, which was 934- and 27-fold greater than the mT-d19/stTR- and pmT-d19/stTR-treated mice, respectively. These results demonstrate that systemic delivery of oncolytic viral genome DNA with liposomes is a powerful alternative to naked Ad, overcoming the limited clinical applicability of conventional Ads and enabling effective treatment of disseminated metastatic tumors.en_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.subjectOncolytic adenovirusen_US
dc.subjectSystemic deliveryen_US
dc.subjectAd genome lipoplexen_US
dc.subjectOrthotopic lung tumor modelen_US
dc.titleViral genome DNA/lipoplexes elicit in situ oncolytic viral replication and potent antitumor efficacy via systemic deliveryen_US
dc.title.alternativelipoplexes elicit in situ oncolytic viral replication and potent antitumor efficacy via systemic deliveryen_US
dc.typeArticleen_US
dc.relation.no2-
dc.relation.volume155-
dc.identifier.doi10.1016/j.jconrel.2011.06.014-
dc.relation.page317-325-
dc.relation.journalJOURNAL OF CONTROLLED RELEASE-
dc.contributor.googleauthorKwon, Oh-Joon-
dc.contributor.googleauthorKang, Eunah-
dc.contributor.googleauthorKim, Sungwan-
dc.contributor.googleauthorYun, Chae-Ok-
dc.relation.code2011204927-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF ENGINEERING[S]-
dc.sector.departmentDEPARTMENT OF BIOENGINEERING-
dc.identifier.pidchaeok-
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