Biomimetic delivery of a STING agonist via tumor antigen-primed dendritic cell membrane nanovesicles for bladder cancer immunotherapy.

STING agonists hold considerable promise for cancer immunotherapy, but their therapeutic efficacy is often limited by poor cellular delivery, rapid systemic clearance, and insufficient activation of antigen-presenting cells. Here, we report an engineered dendritic cell membrane-derived nanovesicle platform (Ag-DCNV-STINGa) for biomimetic delivery of a STING agonist in bladder cancer immunotherapy. Generated from tumor antigen primed mature human monocyte-derived dendritic cell membranes, Ag-DCNV-STINGa preserves key antigen-presentation features and enables stable surface anchoring of 2'3'-cGAMP. Ag-DCNV-STINGa efficiently enhances STING agonist uptake by dendritic cells, promotes dendritic cell activation, and amplifies downstream T-cell-mediated antitumor immunity in vitro. In immunity humanized NSG mice, systemic administration of Ag-DCNV-STINGa exhibits favorable biosafety, suppresses tumor growth in subcutaneous and orthotopic bladder cancer models, and reduces lung metastatic burden. Mechanistically, Ag-DCNV-STINGa reshapes the tumor immune microenvironment by enhancing immune cell infiltration, sustaining interferon-associated immune activation, and promoting the formation of tertiary lymphoid structure-like immune aggregates. Together, these findings establish Ag-DCNV-STINGa as a biomimetic immunoengineering platform that integrates dendritic cell membrane functionality, tumor antigen information, and STING pathway activation to potentiate antitumor immunity. This strategy provides a promising approach for bladder cancer immunotherapy and may offer a broadly applicable framework for the delivery of innate immune agonists in cancer treatment.