Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer
Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer
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DOI：
10.1038/ncomms4545
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发表时间：
2014-04-01
影响因子：
16.6
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Nomoto, Takahiro;Fukushima, Shigeto;Kataoka, Kazunori
对光有反应的纳米载体具有很大的精确治疗潜力，最近的研究显示了有希望的体内活性。然而，光选择性基因转移在系统应用中仍然具有挑战性。在这里，我们报告系统的光响应纳米载体的基因传递通过ABC型三嵌段共聚物/DNA/树枝状光敏剂的顺序自组装，形成具有三层功能纳米隔室的复合物胶束。DNA包装的核被光敏剂结合的中间层覆盖，该中间层被外部屏蔽壳包围。这种三层结构允许通过全身途径将多步光敏剂和DNA递送到实体瘤中：屏蔽层最大限度地减少与血液组分的不利相互作用，并且光敏剂被递送到内/溶酶体膜以促进胶束的光选择性细胞质易位，实现DNA递送到细胞核中以发挥基因表达。该复合物胶束在培养细胞中显示4100倍的光增强基因表达，并在全身给药后在实体瘤中显示光诱导的体内基因转移。
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 4100-fold photoenhanced gene expression in cultured cells and exhibit light-induced in vivo gene transfer in solid tumours following systemic administration.