The potentiated checkpoint blockade immunotherapy by ROS-responsive nanocarrier-mediated cascade chemo-photodynamic therapy

Checkpoint inhibitors, such as and-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 (HNP)-H-TK-C/D to potentiate the antitumor efficacy of anti-PD-1.1 antibody (aPD-L1). Under light irradiation, (HNP)-H-TK-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.