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

Xinyi Lu, Ziwei Chen, Yang Li, Yuecong Guo, Zhenzhen Wang, Shuhan Zhang, Zhichao Wang, Xin Wang, Susu Gao, Tong Guan, Ru Bai, Mengyu Guo, Huige Zhou, Xingfa Gao, Kai Zhang, Yanyan Cui, Chunying Chen, Yaling Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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 CeOx. 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.

Original languageEnglish
Article number102205
JournalNano Today
Volume55
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Charge transfer
  • Immune checkpoint blockade
  • Tumor immunotherapy
  • Ultrasmall AuCe Nanozyme

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