Morphology- and adhesion-dual biomimetic nanovaccine boosts antigen cross-presentation through subcellular transport regulation.

Abstract

In situ tumor vaccines have immense potential for immunotherapy because they generate whole tumor-derived antigens (TDAs) to activate antitumor immune responses. However, the rapid degradation and clearance of the released TDAs severely hinder subsequent antigen presentation and the final efficacy of the in situ vaccine. Here, we synthesized gold nanoxanthium coated with polydopamine (AuNX-PDA) to mimic the morphological and biological adhesion properties of xanthium and mussels, respectively. AuNX-PDA facilitated effective absorption of released TDAs after near-infrared II photothermal treatment and delivery of the absorbed TDAs to the endoplasmic reticulum and Golgi apparatus of dendritic cells for cross-presentation, thereby activating CD8⁺ T cells for efficient tumor-specific immunity. The nanovaccine (NV) significantly inhibited irradiated primary tumors and nonirradiated distant tumors by producing robust antitumor immune responses in B16F10 melanoma and 4T1 breast cancer mouse models. These findings highlight the potency of morphology- and adhesion-dual biomimetic NVs in whole-tumor vaccine therapy.