肿瘤微环境是纳米药物进入肿瘤深部的天然屏障，直接导致了其在肿瘤部位较低的渗透和摄取能力，严重影响了药效发挥。本研究拟构建新型pH/Cathepsin B逐级响应纳米胶束，利用其在肿瘤微酸环境快速解散促渗透摄取、光动力效应（PDT）调控肿瘤微环境以及溶酶体Cathepsin B响应药物释放，实现多西他赛（DTX）在肿瘤部位的精准递送和光疗化疗联用。该纳米胶束以pH超敏感二嵌段聚合物PEG-PC7A为骨架，DTX通过GFLG多肽连结到聚合物上，四氨基酞菁锌修饰可实现体内肿瘤荧光信号放大和PDT效应。设计的纳米胶束可在肿瘤微环境中快速解散，纳米药物粒径迅速减小并暴露出正电荷，促进纳米药物向肿瘤深部渗透和摄取。PDT可通过清除肿瘤微环境基质细胞降低肿瘤微环境屏障作用，进一步提高药物在肿瘤间隙中的扩散。此外，溶酶体中的Cathepsin B可有效水解释放出聚合物中的游离DTX，快速发挥抗肿瘤作用。

Tumor microenvironment is the natural barrier for nanomedicine to enter the deep region of tumor, which directly leads to their low penetration and uptake in tumor, weakening their efficacy. This research intends to construct novel pH/cathepsin B hierarchical responsive micelles, and utilize their promoted osmotic and uptake effect of rapid micelle dissociation in mild acidic tumor site, modulation of tumor microenvironment by photodynamic (PDT) effect and lysosomal cathepsin B responsive drug release behavior, to achieve precise delivery of docetaxel (DTX) at the tumor as well as combined phototherapy and chemotherapy. The designed micelles are based on an ultra pH-sensitive diblock polymer PEG-PC7A, and DTX is linked to the polymer through GFLG polypeptide. Zinc tetraaminophthalocyanine modification can provide the polymer with amplification effect of flurescence signal and PDT efficacy in tumor. The micelles can rapidly dissociate in the tumor microenvironment, the particle size decreases significantly and expose the positive charge, enhancing the penetration and uptake of polymeric drugs into deep region of tumor. PDT can eliminate the barrier effect of tumor microenvironment by scavenging stromal cells, and further improve the drug diffusion inside the tumor mass. In addition, Cathepsin B in lysosome can effectively hydrolyze and release free DTX from polymer rapidly, maximizing the antitumor efficacy.