Hyaluronic acid-modified taurine-polydopamine nanoparticles for combined photothermal-immunotherapy of gastric cancer through microenvironment regulation

Taurine (TAU) has context-dependent roles in gastric cancer. Although exogenous TAU may promote tumor cell growth in vitro, increasing local TAU availability within the tumor microenvironment may support CD8⁺ T-cell-associated antitumor immunity. Here, we developed hyaluronic acid-modified taurine-polydopamine nanoparticles (H/T/PDA) for combined photothermal-immunotherapy of gastric cancer. PDA served as both a TAU carrier and photothermal agent, while HA modification was designed to improve tumor-associated accumulation. H/T/PDA showed good colloidal stability, ROS/pH/light-responsive TAU release, and efficient photothermal conversion under 808 nm laser irradiation. In vitro, H/T/PDA induced photothermal cytotoxicity against gastric cancer cells and promoted ICD-related CRT exposure. TAU-containing formulations enhanced IFN-γ and IL-2 secretion in primary CD8⁺ T cells, while MFC/CD8⁺ T-cell co-culture experiments suggested a net antitumor effect in an immune-cell-containing system. Mechanistic assays further supported SLC6A6-related TAU uptake and increased local TAU availability after H/T/PDA treatment. In MFC tumor-bearing 615 mice, H/T/PDA combined with NIR irradiation produced the strongest tumor suppression among the tested groups and was associated with increased tumor cytokine levels. Preliminary biosafety evaluation showed no obvious hematological, biochemical, or major organ toxicity during the treatment period. These findings suggest that H/T/PDA may serve as a potential nanoplatform for integrating TAU replenishment, photothermal therapy, and immune-associated tumor microenvironment modulation.