A photodynamically activated nanoplatform relieves glucose-driven immunosuppression to potentiate STING immunotherapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) carries a poor prognosis due to its high invasiveness, strong tendency toward metastasis and recurrence, and limited treatment options. Metabolic reprogramming, particularly abnormal glucose metabolism, is a hallmark of TNBC. This dysregulated metabolic pattern is closely associated with the establishment of an immunosuppressive tumor microenvironment (TME). We designed a self-assembling nanoparticle, DI/Ce6@STF, integrating photodynamic therapy (PDT), glucose metabolism intervention, and cGAS-STING pathway activation to achieve synergistic antitumor effects. Under 660 nm laser irradiation, DI/Ce6@STF NPs induce immunogenic cell death (ICD) while releasing the STING agonist DIABZI, the GLUT1 inhibitor STF-31, and reactive oxygen species (ROS) causing oxidative damage. STF-31-mediated glucose uptake inhibition not only reduces energy supply but also synergistically enhances tumor response to DIABZI-induced cGAS-STING activation, significantly improving the TME. Collectively, DI/Ce6@STF induces potent ICD, promotes dendritic cell maturation, and enhances intratumoral infiltration of CD8