Cancer-Targetable pH-Sensitive Zinc-Based Immunomodulators Combined with Photodynamic Therapy for in Situ Vaccination

A cancer vaccine is a promising immunotherapy modality, but the heterogenicity of tumors and substantial time and costs required in tumor-associated antigen (TAA) screening have hindered the development of an individualized vaccine. Herein, we propose in situ vaccination using cancer-targetable pH-sensitive zinc-based immunomodulators (CZIs) to elicit antitumor immune response against TAAs of patients' tumors without the ex vivo identification processes. In the tumor microenvironment, CZIs promote the release of large amounts of TAAs and exposure of calreticulin on the cell surface via immunogenic cell death through the combined effect of excess zinc ions and photodynamic therapy (PDT). With these properties, CZIs potentiate antitumor immunity and inhibit tumor growth as well as lung metastasis in CT26 tumor-bearing mice. This nanoplatform may suggest an alternative therapeutic strategy to overcoming the limitations of existing cancer vaccines and may broaden the application of nanoparticles for cancer immunotherapy.