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Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

Author

Listed:
  • Takahiro Nomoto

    (Graduate School of Engineering, The University of Tokyo)

  • Shigeto Fukushima

    (Graduate School of Engineering, The University of Tokyo)

  • Michiaki Kumagai

    (Graduate School of Engineering, The University of Tokyo)

  • Kaori Machitani

    (Graduate School of Engineering, The University of Tokyo)

  • Arnida

    (Graduate School of Engineering, The University of Tokyo)

  • Yu Matsumoto

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo)

  • Makoto Oba

    (Graduate School of Biomedical Sciences, Nagasaki University)

  • Kanjiro Miyata

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo)

  • Kensuke Osada

    (Graduate School of Engineering, The University of Tokyo
    Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST))

  • Nobuhiro Nishiyama

    (Chemical Resources Laboratory, Tokyo Institute of Technology)

  • Kazunori Kataoka

    (Graduate School of Engineering, The University of Tokyo
    Graduate School of Engineering, The University of Tokyo
    Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo)

Abstract

Nanocarriers responding to light have great potential for pinpoint therapy, and recent studies have revealed promising in vivo activity. However, light-selective gene transfer still remains challenging in the systemic application. Here we report systemic light-responsive nanocarriers for gene delivery developed through the sequential self-assembly of ABC-type triblock copolymer/DNA/dendrimeric photosensitizer, forming polyplex micelles with three-layered functional nanocompartments. The DNA-packaged core is covered by the photosensitizer-incorporated intermediate layer, which is encompassed by an outer shielding shell. This three-layered structure permits multistep photosensitizer and DNA delivery into a solid tumour by a systemic route: the shielding layer minimizes unfavourable interactions with blood components, and the photosensitizer is delivered to endo-/lysosomal membranes to facilitate light-selective cytoplasmic translocation of the micelles, accomplishing DNA delivery into the nucleus to exert gene expression. The polyplex micelles display >100-fold photoenhanced gene expression in cultured cells and exhibit light-induced in vivo gene transfer in solid tumours following systemic administration.

Suggested Citation

  • Takahiro Nomoto & Shigeto Fukushima & Michiaki Kumagai & Kaori Machitani & Arnida & Yu Matsumoto & Makoto Oba & Kanjiro Miyata & Kensuke Osada & Nobuhiro Nishiyama & Kazunori Kataoka, 2014. "Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4545
    DOI: 10.1038/ncomms4545
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