本发明公开了一种基于穿膜肽的三元基因递送系统及其应用,基于穿膜肽的三元基因递送系统用下述方法制成:将多功能多肽REDV‑G‑TAT‑G‑NLS‑C通过邻二硫吡啶聚乙二醇活性酯连接到八氨基POSS的八个活性位点上,形成星形聚合物;带有正电荷的星形聚合物与带负电的基因通过静电相互作用结合,形成表面带有负电的二元基因递送系统;富含组氨酸的多肽序列与二元基因递送系统通过静电相互作用结合,形成三元基因递送系统。本发明的基于穿膜肽的三元基因递送系统对内皮细胞具有靶向性,同时具有穿膜肽、组氨酸和核定位信号的功能,有利于携带基因高效地进入细胞,有效地进行内涵体逃逸并进入细胞核,从而大大提高基因递送效果。
The invention discloses a ternary gene delivery system based on cell-penetrating peptide and applications of the ternary gene delivery system. The ternary gene delivery system based on the cell-penetrating peptide is prepared by adopting the following method: multifunctional polypeptide REDV-G-TAT-G-NLG-C is connected to eight active sites of octa ammonium POSS (polyhedral oligomeric silsesquioxane) through orthopyridyl disulfide-PEG-NHS ester, and thus a star polymer is formed; the star polymer with positive charges and a gene with negative electricity are bonded through electrostatic interaction, and thus a binary gene delivery system with negative electricity on the surface is formed; a polypeptide sequence rich in histidine and the binary gene delivery system are bonded through electrostatic interaction, and thus the ternary gene delivery system is formed. The ternary gene delivery system based on cell-penetrating peptide provided by the invention has targeting ability for endothelial cells, and has the functions of cell-penetrating peptide, histidine and nuclear localization signals, so that carried genes can efficiently enter cells, the escape from endosome is effectively carried out, the entering of the genes into the cell nucleus is realized, and finally, the gene delivery effect is greatly improved.