Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer.
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.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Takahiro
T
Nomoto
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Shigeto
S
Fukushima
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Michiaki
M
Kumagai
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Kaori
K
Machitani
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Arnida
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Yu
Y
Matsumoto
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Makoto
M
Oba
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kanjiro
K
Miyata
1] Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan [2] Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Kensuke
K
Osada
Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
Nobuhiro
N
Nishiyama
1] Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan [2] Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan [3] Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kazunori
K
Kataoka
D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014162:Transfection / Q000295:instrumentation* / Q000379:methods
D008823:Micelles; D017319:Photosensitizing Agents; D011108:Polymers; D004247:DNA