Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys

Masahiro Ohgidani, Koichi Furugaki, Kentaro Shinkai, Yumi Kunisawa, Keiji Itaka, Kazunori Kataoka, Kenji Nakano

    研究成果: Contribution to journalArticle査読

    10 被引用数 (Scopus)

    抄録

    A block/homo-mixed polyplex micelle, comprising of cationic homo polymer: poly{N′-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} P[Asp(DET)] and block copolymer: polyethylene glycol (PEG)-b-P[Asp(DET)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration. In the present study, we investigated the potential of immunogene therapy by intraperitoneal (i.p.) administration of block/homo polyplex micelles for peritoneal dissemination. For evaluation of transgene expression in vivo, block/homo polyplex micelles showed 12-fold higher level in luciferase expression evaluated by bioluminescence imaging system at 24 h after the i.p. administration compared with block polyplex micelles composed with only PEG-b-P[Asp(DET)] in nude mice bearing peritoneal dissemination. The distribution of block/homo polyplex micelles and intracellular uptake of pDNA was observed in tumor nodules. The tumor growth and the prolonged survival rate for the mice harboring disseminated pancreatic cancer more significantly compared with the mock. The antitumor effect of GM-CSF gene therapy was mediated via the activation of natural killer cells. For safety evaluation, block/homo polyplex micelles indicated almost no adverse events for patho-physical findings and blood examinations in mice and cynomolgus monkeys, although slight increases in serum fibrinogen were observed in the monkey model. In conclusion, block/homo polyplex micelle-based immunogene therapy via i.p. administration may be a safe and effective approach for suppressing intractable peritoneal dissemination.

    本文言語英語
    ページ(範囲)238-247
    ページ数10
    ジャーナルJournal of Controlled Release
    167
    3
    DOI
    出版ステータス出版済み - 5 10 2013

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science

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