Creation of intelligent polymeric micelle nanocapsuls for gene delivery

我们研究了通过嵌段共聚物和质粒DNA络合形成的智能聚合物胶束纳米胶囊，作为非病毒基因载体。嵌段共聚物由亲水性聚乙二醇（PEG）和带正电的聚氨基酸组成。为了提高基因表达的有效性，特别是在体内系统中，需要建立通过在聚合物胶束表面引入先导片段来实现主动靶向的新策略。为此，我们开发了一种嵌段共聚物的合成方案，以实现多种智能功能，即延长血管内的循环，增强血管对组织的渗透，选择性转染到目标组织，由于先导部分而增强细胞摄取，质粒DNA在细胞内的平滑释放等。对质粒DNA长度的广泛适应性和聚合物胶束纳米胶囊的环境责任是克服病毒基因传递系统效能所必需的，实验证实了这一点。该系统不仅在体外系统中表现出较高的转染能力，而且在体内初步实验中也表现出较高的转染能力。这种多智能聚合物胶束纳米胶囊可作为非病毒基因传递系统的通用平台。

We investigated intelligent polymeric micelle nanocapsuls formed through the complexation of block copolymers and plasmid DNA, as non-viral gene vectors. The block copolymers are composed of a hydrophilic polyethylene glycol (PEG) and positively charged polyamino acids. To enhance the efficacy of gene expression, in particular in vivo system, novel strategy for the active targeting which can be realized through the introduction of pilot moiety on the surface of polymeric micelles should be established. For this purpose, we developed a synthetic scheme for block copolymers to employ multi-intelligent functions, i.e., prolonged circulation inside the blood vessel tubes, enhanced permeation from the blood vessel tubes toward tissues, selective transfection to the targeting tissues, enhanced cellular uptake due to the pilot moieties, smooth release of plasmid DNA inside the cells, etc.In addition, a wide adaptability for the length of plasmid DNA and also the environmental responsibility of the polymeric micelle nanocapsuls that should be essential to overcome the efficacy of viral gene delivery system were experimentally conformed. This system exhibits highly transfection potency not only in in vitro system but also in preliminary in vivo experiments. This multi-intelligent polymeric micelle nanocapsuls can be treated as an universal platform of non-viral gene delivery system.