有针对性地共运载多种药物是治疗癌症具有综合协同作用所必需的。用少量的药物载体进行多药物输送是有价值的。本文中，我们开发了一个以环状RGD为修饰的纳米粒子（cRGD-TDA）作为多肽运输体，其中包含了阿霉素作为细胞毒性药物，阿苯达唑作为抗转移药物，以及D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）作为反应性氧化物诱导剂，与pH敏感的键结合。然后将这些纳米粒子与PD-L1拮抗剂结合起来治疗4T1三阴性乳腺癌。cRGD-TDA纳米粒子实现了肿瘤靶向的三重药物共运载和pH敏感的三重药物共释放。cRGD-TDA纳米粒子与PD-L1拮抗剂相结合，比单药治疗更明显地抑制了肿瘤生长和转移，这是由于它们的综合协同作用。研究发现TPGS具有强大的免疫原性细胞死亡效应。同时，PD-L1拮抗剂缓解了免疫抑制环境，并与cRGD-TDA纳米粒子具有协同作用。该研究提供了一种治疗难治性癌症的新策略，实现了综合协同治疗。

Targeted co-delivery and co-release of multi-drugs is essential to have an integrative collaborative effect on treating cancer. It is valuable to use few drug carriers for multi-drug delivery. Herein, we develop cRGD-modified nanoparticles (cRGD-TDA) of a conjugate of doxorubicin as cytotoxic agent, adjudin as an anti-metastasis agent and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a reactive oxygen species inducer linked with pH-sensitive bonds, and then combine the nanoparticles with PD-L1 antagonist to treat 4T1 triple-negative breast cancer. cRGD-TDA NPs present tumor-targeted co-delivery and pH-sensitive co-release of triple agents. cRGD-TDA NPs combined with PD-L1 antagonist much more significantly inhibit tumor growth and metastasis than single-drug treatment, which is due to their integrative collaborative effect. It is found that TPGS elicits a powerful immunogenic cell death effect. Meanwhile, PD-L1 antagonist mitigates the immunosuppressive environment and has a synergistic effect with the cRGD-TDA NPs. The study provides a new strategy to treat refractory cancer integratively and collaboratively.