Ultrasmall AuCe nanozyme adjuvant boosted ROS for three-pronged tumor immunotherapy

Catalytic tumor immunotherapy presents a new combination of nanozymes and immunotherapy agents, but the final therapeutic outcomes are usually diminished by insufficient nanozyme activity, immunosuppressive tumor microenvironment (TME), and poor antigen delivery efficiency. Herein, a bimetallic nanozyme-based tumor immunotherapy nanovaccine is first proposed to address these limitations by attenuating the immunosuppression of TME and effectively delivering tumor-specific antigens and catalytic tumor nanomedicine. The tumor-specific antigen OVA-templated bimetallic AuCe nanozyme (denoted as ACO) is a nanodot composed of Au cluster and CeO_x. The high Ce³⁺/Ce⁴⁺ ratio and charge transfer from Au to Ce synergistically enhance the peroxidase-like activity of ACO. The boosted reactive oxygen species level inhibits the proliferation of B16-OVA cells and simultaneously promotes the maturation of dendritic cells. The functionalization of PD-L1 inhibitory D-peptide on ACO (named ACOD) increases tumor targeting specificity and prolongs tumor site retention, facilitating apoptosis of primary and distant tumor cells and conquering immune evasion. Moreover, ACOD catalytic nanovaccine induces long-term immune memory against tumor recurrence and lung metastasis. Therefore, the bimetallic catalytic nanovaccine is a promising nanoformulation to eradicate cancer and safeguard against tumor relapse.