| RRC ID |
44998
|
| 著者 |
Nomoto T, Fukushima S, Kumagai M, Machitani K, Arnida, Matsumoto Y, Oba M, Miyata K, Osada K, Nishiyama N, Kataoka K.
|
| タイトル |
Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
5
|
| ページ |
3545
|
| 公開日 |
2014-4-2
|
| DOI |
10.1038/ncomms4545
|
| PII |
ncomms4545
|
| PMID |
24694458
|
| MeSH |
Animals
Cell Line, Tumor
DNA / chemistry
DNA / genetics*
Female
Genetic Therapy / instrumentation*
Genetic Therapy / methods
Humans
Light
Mice
Mice, Inbred BALB C
Mice, SCID
Micelles
Nanoparticles / chemistry*
Photosensitizing Agents / chemistry
Polymers / chemistry*
Transfection / instrumentation*
Transfection / methods
|
| IF |
12.121
|
| 引用数 |
122
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa |
