Galloyl-Mediated Antigen Capture Coupled with Hypoxia-Responsive Reprogramming Drives Potent Photoimmunotherapy

In situ cancer nanovaccines harness endogenous tumor-associated antigens (TAAs) to address tumor heterogeneity, yet their efficacy is limited by rapid antigen degradation and inefficient lysosomal cross-presentation. Here, we design gallic acid-derived polyphenolic lipids to construct antigen-capturing liposomes (L-GA/INC/PPa) that exploit natural protein-binding properties for enhanced antigen preservation. Compared with covalent maleimide conjugation, noncovalent galloyl groups captured a broader spectrum and higher quantities of tumor antigens. When combined with photodynamic therapy (PDT), L-GA/INC/PPa markedly improved antigen capture, dendritic cell activation, and effector T cell infiltration in melanoma models. Furthermore, PDT-induced tumor hypoxia activated an indoleamine 2,3-dioxygenase-1 (IDO-1) inhibitor prodrug, directly mitigating regulatory T cell expansion triggered by immunogenic cell death. By integration of broad-spectrum antigen presentation with hypoxia-responsive immunosuppression reversal, this dual-modality nanovaccine achieved potent suppression of both primary and distant tumors.