细胞检查点抑制剂已经与化疗联用以提高抗肿瘤效力。然而，克服化疗药物免疫抑制效应仍然是一个挑战。我们在这里报告了一种纳米抗体催化剂结合物Ru-PD-L1，通过将铑催化剂与抗PD-L1纳米抗体融合而成。在Ru-PD-L1和Doxorubicin（DOX）前药一起给药后，Ru-PD-L1能够破坏PD-L1/PD-1的相互作用并催化DOX前药的解封。DOX的局部释放减少了其全身毒性并引发免疫性细胞死亡（ICD）。引发的ICD会触发抗肿瘤免疫反应，并通过PD-L1阻断进一步增强，从而以协同的化疗和免疫疗法抑制潜入肿瘤的T细胞数量增加了49.7％，相比对照组，表现出高度抗肿瘤活性和低细胞毒性在小鼠模型中。与对照组相比，这种联合治疗能够减少小鼠肿瘤的生长率达到67.7％。这种联合方法可以避免化疗药物的负性免疫原性效应，并为人类癌症治疗提供了潜在的化疗免疫疗法策略。

Checkpoint inhibitors have been used with chemotherapy to improve antitumor efficacy. However, overcoming the immunosuppressive effect of chemotherapeutics remains a challenge. We report a nanobody-catalyst conjugate Ru-PD-L1 by fusing a ruthenium catalyst to an anti-PD-L1 nanobody. After administration of Ru-PD-L1 and a doxorubicin (DOX) prodrug, Ru-PD-L1 disrupts the PD-L1/PD-1 interaction and catalyzes the uncaging of the DOX prodrug. The spatially confined release of DOX reduces its systemic toxicity and leads to immunogenic cell death (ICD). The induced ICD triggers antitumor immune responses, which are further amplified by PD-L1 blockade to elicit synergistic chemo-immunotherapy, substantially increasing the number of tumor-infiltrating T-cells by 49.7% compared with the controls, thereby exhibiting high antitumor activity and low cytotoxicity in murine models. The combinational treatment could inhibit the growth of mice tumors by 67.7% compared to the control group. This combinational approach circumvents the negative immunogenic effects of chemotherapeutics and provides a potential chemo-immunotherapy strategy for human cancer treatment.