A novel Au(III) agent designed to inhibit tumor growth and metastasis through inducing immunogenic cell death

Abstract

To treat cancer and inhibit its metastasis to the greatest extent, we proposed to develop an Au(III) agent to induce immunogenic cell death (ICD) and establish long-term immunity. To this end, we optimized a series of Au(III) 2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III) agent (5b) with excellent cytotoxicity to cancer. The results show that 5b effectively inhibits tumor growth and its metastasis in vivo. Interestingly, we revealed a new mechanism of 5b inhibiting tumor growth and metastasis: 5b releases ICD-related damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), ATP and high mobility group box 1 (HMGB1) by inducing endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which then stimulated an antitumor CD8⁺ T cell response and Foxp3⁺ T cell depletion, thus establishing long-action antitumor immunity.

Graphic abstract