An exosome-inspired docetaxel prodrug nanoplatform for potent STING activation and synergistic chemoimmunotherapy.

The treatment of triple-negative breast cancer (TNBC) is significantly hampered by its immunosuppressive tumor microenvironment and limited T-cell infiltration. Activating the STING pathway presents a promising therapeutic avenue due to its potential to trigger a robust innate immune response and remodel the immunosuppressive landscape, thereby sensitizing tumors to immunotherapy. To harness this potential, we developed an exosome-mimetic nanoplatform (EMMDs). EMMDs is fabricated by co-loading a disulfide-linked docetaxel prodrug (DTX-SS-PA) and the STING agonist MSA-2 into polymeric micelles and further decorated with homotypic tumor cell-derived exosomal membrane (EM). This biomimetic design confers superior tumor-targeting capability. Upon reaching the tumor site, the prodrug is specifically activated to release cytotoxic docetaxel (DTX), while MSA-2 is concurrently released to potently activate the STING pathway. This dual action initiates a powerful antitumor immune response and reverses immunosuppression, leading to a synergistic chemo-immunotherapeutic outcome. In the murine TNBC model, EMMDs demonstrated remarkable antitumor efficacy, obviously provoking a robust STING-mediated type I interferon response and inhibiting tumor growth. This work presents a promising biomimetic strategy for remodeling the tumor immune microenvironment via efficient STING activation.