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

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)238-247
    Number of pages10
    JournalJournal of Controlled Release
    Volume167
    Issue number3
    DOIs
    Publication statusPublished - May 10 2013

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    Macaca fascicularis
    Micelles
    Granulocyte-Macrophage Colony-Stimulating Factor
    Genetic Therapy
    Immunity
    Safety
    DEET
    Viperidae
    Transgenes
    Luciferases
    Pancreatic Neoplasms
    Nude Mice
    Natural Killer Cells
    Fibrinogen
    Haplorhini
    Neoplasms
    Polymers
    Therapeutics
    Growth
    Serum

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science

    Cite this

    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. / Ohgidani, Masahiro; Furugaki, Koichi; Shinkai, Kentaro; Kunisawa, Yumi; Itaka, Keiji; Kataoka, Kazunori; nakano, kenji.

    In: Journal of Controlled Release, Vol. 167, No. 3, 10.05.2013, p. 238-247.

    Research output: Contribution to journalArticle

    Ohgidani, Masahiro ; Furugaki, Koichi ; Shinkai, Kentaro ; Kunisawa, Yumi ; Itaka, Keiji ; Kataoka, Kazunori ; nakano, kenji. / 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. In: Journal of Controlled Release. 2013 ; Vol. 167, No. 3. pp. 238-247.
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    AU - Ohgidani, Masahiro

    AU - Furugaki, Koichi

    AU - Shinkai, Kentaro

    AU - Kunisawa, Yumi

    AU - Itaka, Keiji

    AU - Kataoka, Kazunori

    AU - nakano, kenji

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