Bacteria‐Mediated Bismuth‐Based Nanoparticles Activate Toll‐Like Receptors for Breast Cancer Photothermal Immunotherapy

Abstract One of the latest immunotherapeutic strategies involves modulating the tumor microenvironment through Toll‐like receptors (TLRs). However, Toll‐like receptor agonists may induce severe systemic inflammation. Bif@PBi‐R, a bacterial nanomotor is developed with tumor‐targeting properties in this study. Bismuth‐based nanoparticles loaded with R848 (Bi‐R NPs) are bound to anaerobic bifidobacteria via polydopamine adhesion. Bif@PBi‐R is designed to deliver bismuth‐based nanoparticles carrying R848 specifically to the tumor area to activate anti‐tumor immunotherapy. Bismuth is an excellent nanomaterial for photothermal conversion. Therefore, Bif@PBi‐R not only enhances the efficacy of photothermal therapy to kill tumor cells directly but also boosts the anti‐tumor immune response through its photothermal therapeutic effect. Combining Bif@PBi‐R with 808 nm laser irradiation significantly promoted dendritic cell (DCs) maturation, leading to a potent anti‐tumor effect. In summary, this bacterial nanomotor effectively enhances the efficacy of immunotherapy when combined with photothermal therapy (PTT).