为解决靶向递药载体对EPR效应缺失肿瘤与肿瘤深层病灶疗效差的难题，设计了一种“特洛伊木马”式靶向DDS，以表面修饰RGD环肽的单核细胞（MCRGD）为“木马”，内含金纳米棒（GNRs）与阿霉素（DOX）前药。该DDS可逃避MPS吞噬并靶向至肿瘤血管壁；MCRGD受肿瘤分泌的趋化因子作用穿透血管壁并向肿瘤病灶中心迁移；当MCRGD深入肿瘤后，内部的GNRs在激光照射下产生活性氧（ROS），ROS使MC细胞膜泄漏，释放出抗肿瘤前药与GNRs；前药在2种肿瘤特异性酶的共同作用下激活为原药。这种光/酶双重敏感靶向策略可显著提高药物对肿瘤的靶向性和对正常组织的安全性；利用药物的细胞毒性与GNRs的PDT作用深层次联合治疗肿瘤。拟对该靶向DDS的制备纯化、理化性质、释药行为、安全性等进行研究，重点探索其趋化作用、光、酶响应性，体内外靶向性及抗肿瘤功效。本课题实施将为提高肿瘤靶向治疗水平提供有益探索。

To solve the poor effect of tumor-targeted drug delivery system (DDS) on tumors lacking EPR effect and tumorous deep regions, a trojan horse-like DDS was designed. Mononuclear cells with cRGD peptides on the cell membrane surface (MCRGD) were utilized as the “trojan horse” and gold nanorods (GNRs) and DOX prodrugs were loaded into them. This DDS could escape the monitoring of MPS and be targeted to the tumor microvascular wall. MCRGD crossed the endothelial cell wall and migrated to the necrotic center by a chemo-attractive gradient. When drug loaded MCRGD penetrated into tumor tissues, the intracellular GNRs generated ROS. Lysosome membranes and MC membranes were damaged by ROS, hence GNRs and prodrugs were released from the leaking MC cells. The active DOX was co-actived by 2 kinds of enzymes which were specifically expressed in tumor microenvironment. The photo/enzyme dual-sensitive targeting strategy can significantly improve the tumor targeting and the safety to normal tissues of drugs. Then, the combination of the chemotherapy of DOX with the photodynamic therapy of GNRs offered synergistic effects against the tumor cells. The method of preparation and purification, physicochemical property, drug release behavior, and safety of this GNRs/HAD@MCRGD DDS will be studied. Specific emphasis is placed on exploring the chemotactic responsiveness, the light responsiveness, the enzyme responsiveness, the tumor-targeting in vitro and in vivo, and the antitumor efficiency of it. The implementation of this project will provide a valuable exploration to improving the level of tumor targeting therapy.