Low immunogenicity and immunosuppressive tumor microenvironment (TME) are two pivotal factors restricting tumor immunotherapy. Photodynamic therapy (PDT) directly destroys cancer cells by producing reactive oxygen species (ROS), and enhances the immunogenicity of "cold" tumors by inducing immunogenic cell death (ICD), thereby promoting T cell development against tumors. However, PDT also deteriorates immunosuppression through overactivating the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. To this end, biocompatible albumin nanoassemblies co-delivering IR780 and diclofenac are herein developed for enhanced therapy against triple-negative breast cancer. PDT-exacerbated PGE2 overexpression is effectively abolished by diclofenac-mediated COX-2 inhibition, which reprograms immunosuppressive TME