本项目设计了基于DNA纳米团的靶向型聚离子复合物（PIC）胶束用于siRNA的递送及抗肿瘤研究。该PIC胶束由iRGD配体偶联的聚乙二醇—聚天冬氨酸（四乙烯五胺）嵌段聚合物（iRGD-PEG-b-PAsp(TEP)）与表面接枝siRNA的DNA纳米团（DNAnc-g-siRNAs）通过静电作用制备而成。该新型PIC胶束充分利用DNAnc-g-siRNA高负电荷特性，成功解决了传统PIC胶束由于siRNA携带负电荷少，与阳离子聚合物静电相互作用弱、血液稳定性差这一问题，可望得到长血液循环的siRNA纳米药物。该PIC胶束进入细胞后，DNA纳米团表面的siRNA易被Dicer酶剪切，siRNA得到高效释放。此外，该PIC胶束结合了目前siRNA递送体系的一些优良特性，如主动靶向和“质子海绵”效应等功能。因此，该新型PIC胶束可望取得较好的RNAi效果，实现安全高效的siRNA纳米药物肿瘤治疗。

In this project, we design a novel targeted polyion complex (PIC) micelle base on DNA nanoclew for siRNA delivery and cancer therapy. This new PIC micelle would be prepared by the electrostatic interaction between internalizing RGD (iRGD) installed poly(ethylene glycol)-b- poly[N′′′-(N′′-{N′-[N-(2-aminoethyl)-2- aminoethyl]-2-aminoethyl}-2-aminoethyl)aspartamide] (iRGD-PEG-b-PAsp(TEP) block copolymer and DNA nanoclew grafted with siRNA (DNAnc-g-siRNAs). In comparison with conventional PIC micelle that display blood instability due to its weak electrostatic interaction between polycation and low negative-charged siRNA, the newly formed PIC micelle because make full use of the high negative charge feature of DNAnc-g-siRNAs, would exhibit long blood circulation time. Furthermore, these siRNAs on DNA nanoclew surface would be cleaved by Dicer enzyme after been taken up by cells, resulting in effective siRNA release. Moreover, this novel PIC micelle combines some superior functionality (such as active targeting, “proton sponge” effect) of nowadays siRNA delivery systems. So this novel PIC micelle would be expected to achieve potent RNAi, and would be a safe and effective siRNA nanomedicine for caner therapy.