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

Takahiro Nomoto, Shigeto Fukushima, Michiaki Kumagai, Kaori Machitani, Arnida, Yu Matsumoto, Makoto Oba, Kanjiro Miyata, Kensuke Osada, Nobuhiro Nishiyama () and Kazunori Kataoka ()
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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
Nobuhiro Nishiyama: Chemical Resources Laboratory, Tokyo Institute of Technology
Kazunori Kataoka: Graduate School of Engineering, The University of Tokyo

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4545

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