Fig. 1. Schematic diagram integrating TRIM-targeted antibacteria with antitumor therapies.

a The aggravated immunosuppression induced by TRIM in the TME, where the presence of TRIM upregulates the expression of IL-17, TGF-β, and IL-10 while downregulates PD-1, TNF-α, IL-1β, IL-12, and IFN-γ, reducing the number of T cells and M1-like type TAMs but increasing M2-like type TAMs. b Simultaneous TRIM-targeted antibacteria and multimodal antitumor therapy (CDT, PTT, and chemotherapy) enabled by a single agent, i.e., the Ag₂Se shell covered-Au NPs equipped with folic acid (Au@Ag₂Se-FA): the released Ag ions and Fenton-like reaction of Ag NCs evolved upon NIR irradiation endow antibacteria together with chemotherapy and CDT to inhibit both the TRIM and tumor cells; the high extinction coefficient and photothermal conversion efficiency of Au@Ag₂Se-FA allow significant hyperthermia to eliminate cancer cells (PTT). The combination upregulates PD-1, IL-17, TNF-α, IFN-γ, and IL-1β, downregulates IL-10 and TGF-β, releases HSP-70 in the TME, activates the immune response of T cells, and promotes the repolarization of TAMs from the M2- to M1-like phenotype.