Migrasomes constrained by a homologous-targeting photodynamic nanoplatform: enhancing intratumoral CD8

Photodynamic therapy (PDT) is an effective adjunct treatment for oral squamous cell carcinoma (OSCC). Enhancing photosensitizer targeting and inducing effective cytotoxic T-cell responses through photoimmunotherapy have become key strategies to improve PDT efficacy. Migrasomes, as vesicular structures assembled by TSPAN4 and cholesterol microdomains, are implicated in immune escape and are emerging as sensitization targets for PDT. Here, we report a biomimetic nanoplatform, MOF-919@CCM, that combines enhanced tumor-cell membrane adhesion with light-controlled cholesterol degradation. Cloaking with a homologous cancer-cell membrane (CCM) imparts specific adhesion to tumor cells and improves targeted delivery of the photosensitizer. Moreover, the transition-metal nodes of MOF-919 exhibit peroxidase- and catalase-like activities that alleviate tumor hypoxia and, under laser irradiation, effectively reduce cellular cholesterol levels. Experiments further revealed that PDT based on MOF-919@CCM markedly suppresses migrasome formation via effective degradation of cholesterol and promotes CD8⁺ T-cell infiltration and cytotoxic activity against tumor cells. This work develops a targeted PDT approach using MOF-919@CCM and provides a new strategy for the immunotherapy of OSCC.