Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in a mouse tumor model

Lin Cui, Kensuke Osada, Akira Imaizumi, Kazunori Kataoka, Kenji Nakano

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    In this study, the potential of DNA vaccine by subcutaneously (s.c.) administered block/homo-mixed (B/H) polyplex micelles carrying genes encoding tumor-associated antigen SART3 as well as CD40L and GM-CSF was compared with the intraperitoneal (i.p.) and intravenous (i.v.) administrations or electroporation method. Confocal laser microscopy revealed high localization of polyplexes in groin lymph nodes and local skin tissues after s.c. administration, and in the mesenteric lymph nodes, liver, and spleen after i.p. administration, but not after i.v. administration. Real-time RT-PCR and immunohistochemistry showed transgene expression in the above organs by s.c. and i.p. administered B/H polyplex micelles, but not by the i.v. administration or electroporation. Polyplex-carried DNA vaccines significantly decreased the weight of subcutaneous CT26 tumors in mice compared to the mock (2.9 ± 0.8 vs 6.4 ± 2.6 g, P < 0.05 for s.c.; 3.2 ± 1.1 vs 4.7 ± 2.1 g, P < 0.05 for i.p. administration). The survival rate was improved by s.c. administration of the DNA vaccine (P < 0.05) and by the i.p. administered DNA vaccine (P < 0.01) compared with that of the mock controls in mice with peritoneally disseminated CT26 cancer. Such therapeutic effects were not observed by the naked DNA, i.v. administered DNA vaccine or electroporation. CTL and NK cell activities of splenocytes and infiltration of CD11c+ DCs, and CD4+ and CD8a+ T cells into tumor tissues were upregulated in the s.c. administered DNA vaccine group (P < 0.05), which was consistent with i.p. administration. No abnormal findings in local injection sites, body weight, or blood examinations were observed by s.c. or i.p. administration of polyplex micelles, whereas proinflammatory cytokine production was minimized in visceral organs with the s.c. administered polyplex-carried DNA vaccine. In conclusion, s.c. administration of B/H polyplex micelles may be a safe and useful modality for DNA vaccination.

    Original languageEnglish
    Pages (from-to)220-231
    Number of pages12
    JournalJournal of Controlled Release
    Volume206
    DOIs
    Publication statusPublished - May 28 2015

    Fingerprint

    DNA Vaccines
    Micelles
    Vaccination
    DNA
    Electroporation
    Neoplasms
    Intravenous Administration
    Confocal Microscopy
    Lymph Nodes
    CD40 Ligand
    Groin
    Neoplasm Antigens
    Therapeutic Uses
    Granulocyte-Macrophage Colony-Stimulating Factor
    Transgenes
    Natural Killer Cells
    Real-Time Polymerase Chain Reaction
    Spleen
    Immunohistochemistry
    Body Weight

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science

    Cite this

    Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in a mouse tumor model. / Cui, Lin; Osada, Kensuke; Imaizumi, Akira; Kataoka, Kazunori; Nakano, Kenji.

    In: Journal of Controlled Release, Vol. 206, 28.05.2015, p. 220-231.

    Research output: Contribution to journalArticle

    Cui, Lin ; Osada, Kensuke ; Imaizumi, Akira ; Kataoka, Kazunori ; Nakano, Kenji. / Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in a mouse tumor model. In: Journal of Controlled Release. 2015 ; Vol. 206. pp. 220-231.
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    abstract = "In this study, the potential of DNA vaccine by subcutaneously (s.c.) administered block/homo-mixed (B/H) polyplex micelles carrying genes encoding tumor-associated antigen SART3 as well as CD40L and GM-CSF was compared with the intraperitoneal (i.p.) and intravenous (i.v.) administrations or electroporation method. Confocal laser microscopy revealed high localization of polyplexes in groin lymph nodes and local skin tissues after s.c. administration, and in the mesenteric lymph nodes, liver, and spleen after i.p. administration, but not after i.v. administration. Real-time RT-PCR and immunohistochemistry showed transgene expression in the above organs by s.c. and i.p. administered B/H polyplex micelles, but not by the i.v. administration or electroporation. Polyplex-carried DNA vaccines significantly decreased the weight of subcutaneous CT26 tumors in mice compared to the mock (2.9 ± 0.8 vs 6.4 ± 2.6 g, P < 0.05 for s.c.; 3.2 ± 1.1 vs 4.7 ± 2.1 g, P < 0.05 for i.p. administration). The survival rate was improved by s.c. administration of the DNA vaccine (P < 0.05) and by the i.p. administered DNA vaccine (P < 0.01) compared with that of the mock controls in mice with peritoneally disseminated CT26 cancer. Such therapeutic effects were not observed by the naked DNA, i.v. administered DNA vaccine or electroporation. CTL and NK cell activities of splenocytes and infiltration of CD11c+ DCs, and CD4+ and CD8a+ T cells into tumor tissues were upregulated in the s.c. administered DNA vaccine group (P < 0.05), which was consistent with i.p. administration. No abnormal findings in local injection sites, body weight, or blood examinations were observed by s.c. or i.p. administration of polyplex micelles, whereas proinflammatory cytokine production was minimized in visceral organs with the s.c. administered polyplex-carried DNA vaccine. In conclusion, s.c. administration of B/H polyplex micelles may be a safe and useful modality for DNA vaccination.",
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    AU - Osada, Kensuke

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    AU - Kataoka, Kazunori

    AU - Nakano, Kenji

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