Biomimetic delivery of a STING agonist

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.