重要脏器的纤维化严重威胁人类健康，涉及非意外死亡的35%以上，且迄今未见除器官移植外的其他有效治疗方案。近年来，利用RNA干扰技术调节基因表达被认为是抑制纤维化的有效策略，但其面临的挑战是“高转染效率-低生物毒性”的平衡以及高靶向性。本项目拟使用天然生物纳米粒子为基体，结合血小板，构建小干扰RNA靶向输送体系。利用天然生物纳米粒子高转染效率和无免疫原性副反应的优势，结合血小板对损伤部位的高度趋向性，通过酶响应多肽完成血小板定点脱除，实现递送系统的精准靶向和高转染效率。系统研究生物纳米粒子表面电荷、表面多肽比例对RNA干扰系统稳定性、生理毒性、体内分布、RNA干扰效率、及纤维化抑制性能的影响，并建立构效关系。项目发挥天然材料的优势，构建定位精准可控、兼具高转染效率和低生物毒性的小干扰RNA靶向输送体系并研究其生物作用，为实现抑制纤维化的RNA干扰提供新策略。

Fibrosis of vital organs threatens human health seriously, and relates to more than 35% non-accidental deaths. There is no effective strategy to cure the formed fibrosis in vital organs but organ transplantation. Recently, regulation of gene expression through RNA interference has been proven an efficient way to inhibit fibrosis. But the targeted delivery of small interfering RNA (siRNA) with high efficiency and low cytotoxicity is a key challenge. In this project, we propose to construct an siRNA delivery system from natural bionanoparticle and platelets. By taking advantage of the high transferring efficiency/no immunogenic side effect of bionanoparticles, and the natural tendency towards injuries of platelets, in addition with the enzyme responsive departure of platelet at specific sites, this siRNA delivery system can achieve precise targeting property and high transferring efficiency. The effect of surface charge, peptide ratio on the system stability, cytotoxicity, biodistribution, RNA interference efficiency and fibrosis inhibition capacity will be systematically investigated, and the structure-activity relationships will be established. This project fully exploits the superiority of natural biomaterials to construct siRNA delivery systems, which behave precise targeting property, high transferring efficiency and low cytotoxicity, and may provide new strategies for the RNA interference on fibrosis inhibition.