Engineered T cell membrane coated nanoparticles reverse thermo-resistance and reprogram tumor microenvironment to synergistically potentiate bladder cancer photothermal immunotherapy.

Immunotherapy has made a breakthrough in the treatment of advanced bladder cancer, but the immunosuppressive tumor microenvironment (TME) leads to unsatisfactory clinical outcome. Photothermal therapy (PTT) is an emerging approach to synergistically enhance tumor immunotherapy, but its therapeutic efficacy suffers from insufficient distribution of photothermal agents and tumor thermo-resistance. Here, we have developed engineered T cell membrane coated triptolide-loaded polydopamine nanoparticles (ETM@PT), which exhibited excellent biocompatibility and tumor targeting properties. ETM@PT decreased heat shock proteins expression, inhibited cancer associated fibroblasts activation and downregulated MMP9 levels, demonstrating superior tumor suppression effects in multiple mouse bladder cancer models and synergistically enhancing anti-PD1 immunotherapy effectively. RNA sequencing further revealed the molecular mechanism of ETM@PT activating immune-related pathways and amplifying antitumor immunity. This strategy effectively reversed thermo-resistance and reprogrammed the immunosuppressive TME, representing a promising approach to clinical advanced bladder cancer therapy.