Self‐Propelled In Situ Polymerized Nanoparticles Activating the STING Pathway for Enhanced Bladder Cancer Immunotherapy

Abstract Bladder cancer, a common malignancy of the urinary tract, presents complex therapeutic challenges, thereby necessitating the exploration of innovative treatment strategies. This study introduces a novel, self‐propelled nanomedicine delivery system that forms nanoparticles within the bladder lumen by co‐infusing dopamine hydrochloride, Mn 2+ , cGAMP, and urease into the bladder to initiate in situ polymerization. The resulting Mn‐cGAMP@PDA‐urease (DMCU) nanoparticles possess a urease‐modified surface, which acts as an engine to generate propulsive force by breaking down urea. Consequently, this process enhances nanoparticle retention in the bladder mucosa and facilitates efficient drug delivery. The self‐assembled nanoparticles activate the STING pathway, promoting dendritic cell maturation and activation of T cells, thereby enhancing anti‐tumor immune responses. These nanoparticles remain in the bladder for an extended period, significantly improving therapeutic efficacy by sustaining drug release and reducing adverse side effects. In vivo, experiments using a mouse orthotopic model of bladder cancer demonstrate that the DMCU system enhances tumor suppression and immune activation compared with conventional therapies. This novel approach integrates nanotechnology with immunomodulation to address chemotherapy resistance and improve therapeutic efficacy.