舒尼替尼是目前治疗晚期肾癌的一线药物，其应用过程中产生的耐药问题和不良反应问题是临床亟待解决的两个难题。研究表明溶酶体对舒尼替尼的隔离作用和舒尼替尼缺乏对肾癌细胞的靶向性分别为耐药问题和不良反应问题产生的原因。申请人前期成功构建具有有效溶酶体逃逸功能的纳米多肽胶束应用于泌尿系统肿瘤，文章发表于Journal of Controlled Release（IF 7.7）。在此基础上，以核苷酸适体AS1411为特异性靶头，首次构建兼有肾癌细胞靶向性和有效溶酶体逃逸功能的纳米多肽胶束AS1411-PEG-SHRss，并利用其包载舒尼替尼，实现舒尼替尼的有效溶酶体逃逸和在肾癌细胞的靶向分布。本研究将考察载有舒尼替尼的纳米多肽胶束对肾癌细胞的靶向性、抗耐药肾癌细胞作用、对自噬的影响、胞内转运/溶酶体逃逸、体内作用及安全性，拟为临床解决晚期肾癌治疗过程中舒尼替尼的耐药问题和不良反应问题提供新的思路。

Sunitinib is the first-line drug in the treatment of advanced renal carcinoma. The problems of drug resistance and adverse reactions needed to be solved urgently. Studies have shown that drug resistance and adverse reactions resulting from lysosome isolation of sunitinib and the lack of targeting. Polypeptide micelles with the function of effective lysosome escape have successfully constructed for the treatment of urinary tract tumors which published in Journal of Controlled Release (IF 7.7). Polypeptide micelles AS1411-PEG-SHRss which possess both renal cancer cell targeting and effective lysosome escape function will be constructed based on previous study. Sunitinib will be loaded into AS1411-PEG-SHRss in order to achieve effective lysosome escape and targeted distribution in renal carcinoma. In this study, the targeting ability of AS1411-PEG-SHRss/sunitinib, anti-proliferative efficacy against sunitinib-resistant renal cell carcinoma, autophagy, intracellular transport/lysosome escape, in vivo efficacy and safety will be investigated. Finally, this study will provide new ideas to solve the problems of drug resistance and adverse reactions of sunitinib during the treatment of advanced renal cell carcinoma.