GGT-targeting polysarcosine-decorated CaCO₃ nanoplatform for ICD-enhanced breast cancer immunotherapy

Immunogenic cell death (ICD) as emerging cancer immunotherapy has received growing interests owing to in situ producing plenty of tumor associated antigens (TAAs) and activating the immune system. However, precise induction of the ICD and transforming immunologically inert tumor into immunologically active tumor remain a critical hurdle in the field. Herein, programmed γ-glutamyl transpeptidase (GGT)-targeting CaCO₃ nanoparticles (DGPSCa) with dual encapsulation of ICG and 5-carboxy-8-hydroxyquinoline (IOX1) are facilely prepared by gas diffusion and surface modification with GGT-targeting polysarcosine. After targeting tumor-overexpressed GGT and upon mild 808 nm laser irradiation, these DGPSCa are highly uptaken by 4 T1 tumor cells, precisely release ICG and IOX1 upon intracellular environment, and generate abundant reactive oxygen species (ROS), resulting in robust ICD effect as well as the downregulation of the PD-L1. After i.v. administration, these DGPSCa can highly accumulate in tumor and significantly inhibit tumor growth by effectively boosting immune system and reducing immunosuppressive tumor environment.