131I-labeled engineered hybrid cell membrane biomimetic nanocarrier targets gastric cancer and enhances radioimmunotherapy.

Achieving efficient radiolabeling and targeted delivery is essential to maximize therapeutic efficacy and reduce systemic toxicity. Herein, we report a novel radionuclide-delivery platform based on hybrid membranes derived from fusing liposome with statherin engineered macrophage membranes and gastric cancer cell (MFC) membranes. The obtained 131I-lipo@[RAW-MFC] nanoparticles (131I-LipRM) exhibit high-yield, stable radiolabeling and homologous tumor targeting. Using a gastric cancer model, we assess the biodistribution and therapeutic potential of 131I-LipRM alone and combine with anti-PD-L1 therapy. 131I-LipRM show favorable pharmacokinetics and efficient tumor localization, inducing significant tumor cell damage and growth suppression. Furthermore, the combination of 131I-LipRM with anti-PD-L1 therapy has synergistically enhanced T cell-mediated immune responses, promoted CD8+ T cell infiltration, and prolonged survival relative to monotherapies. These findings demonstrate that the 131I-LipRM platform enables precise radionuclide delivery and potentiates antitumor immunity through PD-L1 blockade, presenting a promising avenue for radio-immunotherapy.