A trinity Strategy: Mesoporous platinum nanoparticles serve as a photoenhanced nanoplatform for tumor immunotherapy

Combination cancer therapy could maximize the benefits of immunotherapy by remodeling the tumor microenvironment. Platinum has been used in cancer therapy due to its unique antitumor, photothermal and catalytic properties. Herein, we successfully developed a mesoporous platinum nanoparticle (mPt)-based trinity strategy nanoplatform for enabling synergistic photodynamic therapy (PDT), photothermal therapy (PTT) and immunotherapy. Specifically, platinum nanoparticles were first fabricated and decorated with a silica shell for photosensitizer hematoporphyrin monomethyl ether (HMME) conjugation and further coated with a thermosensitive lipid bilayer containing an immune adjuvant resiquimod (R848), resulting in a multifunctional nanoplatform (RH@PSN@Lip). The visible red laser activation not only directly killed tumor cells but also induced tumor immunogenic cell death (ICD). mPt also served as a nano-enzyme to alleviate the hypoxic microenvironment of tumors and generated oxygen for PDT. Furthermore, the visible red laser served as a "switch" to trigger the release of R848 from the lipid bilayer of RH@PSN@Lip, thereby strengthening anti-tumor immune responses and remodeling the tumor microenvironment. Collectively, this trinity strategy nanoplatform successfully increased tumor-infiltrating lymphocytes and reversed the suppressive condition in the tumor microenvironment. Consequently, melanoma growth was remarkably inhibited, and mice were also protected from tumor rechallenging. Overall, this work presents an innovative and promising synergistic therapeutic strategy for clinical cancer treatment.