申请人近年来主要集于纳米药物载体调控抗肿瘤药物活性及其协同效应的研究。代表性成果包括：①采用纳米药物载体调控药物的透皮传输行为，提高药物治疗指数；②构建新型功能化纳米药物载体，调控抗肿瘤药物的靶向性及亚细胞转运行为，增强其抗肿瘤活性；③进一步探索并阐明纳米药物载体在增强肿瘤光热治疗及其协同效应中的关键作用。本项目拟合成生物可降解的新型聚氨基酸材料，构建pH响应的交联型载药聚合物纳米囊泡，用于光热治疗药物与分子靶向药物之间的双向协同增效治疗。作为第一/通讯作者，在 J. Am. Chem. Soc., ACS Nano, Biomaterials, Theranostics, J. Control. Release等杂志发表SCI论文15篇，其中9篇影响因子大于7，他引437次, 单篇最高他引95次；作为第一发明人，获得中国发明专利1项。

The applicant focuses on the nanocarriers for cancer therapy and thereof synergistic effect. The representative results are as follows: (1) The nanocarriers were constructed to regulate the skin permeation behaviors of drugs for enhanced therapeutic index. (2) The novel functionalized nanocarriers were developed to optimize the cancer targeting and subcellular translocation of drugs for superior anticancer efficiency. (3) We further elucidated that the nanocarriers play a key role in photothermal cancer therapy and thereof synergistic effect. In this project, we propose to synthesize biodegradable poly(amino acid)-based polymer, which is used to construct pH-responsive cross-linked drug-loaded polymeric nanovesicles for bidirectionally synergistic effects between photothermal and molecularly targeted therapies. The applicant as the first and corresponding author has published 15 papers on J. Am. Chem. Soc., ACS Nano, Biomaterials, Theranostics, and J. Control. Release including 9 papers with impact factors of at least 7. These papers have been cited by the others for 437 times, and the highest citation for single paper has reached 95 times. The applicant has an authorized Chinese invention patent as the first inventor as well.

课题负责人重点构建了多功能、响应性高分子载体，增强药物的光热治疗作用，并通过胞浆转运和响应释药设计，克服药物的胞内传输屏障，发展出高效的肿瘤热疗与其它疗法（如分子靶向治疗等）等的协同治疗策略。纳米粒在肿瘤微环境刺激下可响应性释放药物，并通过碳菁染料产生的活性氧自由基（ROS）破坏溶酶体促进胞浆转运，从而增强分子靶向药物如17AAG的分子靶向治疗效应；同时，分子靶向药物17AAG可有效抑制肿瘤细胞受热应激性过表达的热休克蛋白90，从而降低细胞的热耐受性，进而增强碳菁染料光热效应对肿瘤细胞的光热损伤作用。这种双向协同增效通过更强的细胞凋亡和坏死效应，显著提升了纳米粒对肿瘤细胞的协同治疗效应，实现了肿瘤的消融。在本项目的支持下，课题负责人作为通讯作者在Adv Mater、ACS Nano、Adv Funct Mater等高水平国际期刊发表SCI论文18篇，其中影响因子大于10的论文14篇，项目编号第一标注论文12篇，ESI高被引论文1篇，封面论文1篇。撰写Wiley、Springer出版社出版的英文专著各1章，作为副主编参编教材《药剂学》1本。申请中国发明专利4项，2016年入选教育部“长江学者奖励计划”青年学者。