Antigen‐Enriched Hydrogel Platform Coordinates Hydrogen Sulfide and Bacterial Adjuvants for Augmenting the Photothermal Immunotherapy of Breast Cancer

Abstract Photothermal therapy (PTT) can release breast cancer antigens and activate immune responses, but its systemic efficacy is limited by rapid antigen clearance, dendritic cells (DCs) dysfunction, and neutrophil extracellular traps (NETs) formation. To address this, we developed a multimodal hydrogel platform (CuS@BDV/TA gel) containing copper sulfide nanoparticles (CuS NPs), bacterial‐derived vesicles (BDV), and tannic acid (TA). Under near‐infrared irradiation, CuS NPs mediate PTT to release antigens, which are then captured by TA to form an in situ antigen library for sustained antigen‐presenting cell stimulation. BDV and hydrogen sulfide (H 2 S) from CuS NPs restore DCs function via pattern recognition receptor activation and cGAS‐STING pathway activation. BDV also reprograms macrophage polarization, while H 2 S suppresses NETs formation. This gel potently activates intratumoral DCs, expands CD8 + T cells (including granzyme B‐expressing and IFN‐γ‐expressing CD8 + T cells) and NK cells, and reduces immunosuppressive cell populations. In mouse models, the strategy enhances ablation of primary breast tumors and inhibits lung metastasis. Overall, this “kill four birds with one stone” hydrogel extends antigen retention, improves DCs presentation, remodels the immunosuppressive microenvironment, and inhibits NETs, offering a new paradigm for breast cancer immunotherapy.