Checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have been proven as a promising type of immunotherapy in a number of cancers, but the relatively low response rates limit their scope of clinical application. Here, we report the use of cascade chemo-photodynamic therapy (chemo-PDT) with reactive oxygen species (ROS)-sensitive lipid-polymer hybrid nanoparticles ^TKHNP-C/D to potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1). Under light irradiation, ^TKHNP-C/D not only induced photodynamic therapy (PDT) but also boosted intracellular DOX release via the rapid degradation of its hydrophobic core, promoting an efficient cascade of chemo-PDT to inhibit tumor growth by a single treatment. More importantly, the cascade chemo-PDT could evoke anticancer immune responses and efficiently synergize with aPD-L1 to generate an abscopal effect, which could simultaneously inhibit primary and distant tumor growth.

检查点抑制剂，例如抗-PD-1 / PD-L1抗体，已被证明是许多癌症中一种有前途的免疫疗法，但是相对较低的应答率限制了其临床应用范围。在这里，我们报告了级联化学光动力疗法（chemo-PDT）与活性氧（ROS）敏感的脂质-聚合物杂化纳米颗粒^TK HNP-C / D的使用，以增强抗-PD-L1抗体的抗肿瘤功效（ aPD-L1）。在光照射下，^TK HNP-C / D不仅诱导了光动力疗法（PDT），而且还通过以下途径增强了细胞内DOX的释放：疏水核心的快速降解，通过单一治疗促进了化学PDT的有效级联，从而抑制了肿瘤的生长。更重要的是，级联化学PDT可以引起抗癌免疫反应，并与aPD-L1有效协同产生明显的效应，从而可以同时抑制原发性和远处的肿瘤生长。