Developing a Novel Anticancer Gold(III) Agent to Integrate Chemotherapy and Immunotherapy

Abstract

To effectively treat gastric cancer, we innovatively attempted to develop a metal agent to integrate immunotherapy and chemotherapy by dual targeting the cellular components in the tumor microenvironment (TME) based on the specific residue of human serum albumin (HSA) nanoparticles (NPs). We synthesized a series of Au(III) α-N-heterocyclic thiosemicarbazone compounds and obtained a Au agent (<b>5b</b>) with remarkable cytotoxicity to gastric cancer cells; moreover, we successfully constructed a novel <b>HSA-5b</b> complex NP delivery system. Importantly, the <i>in vivo</i> results showed that <b>5b</b>/<b>HSA-5b</b> NPs effectively inhibited gastric tumor growth and <b>HSA-5b</b> NPs enhanced the therapeutic efficiency, bioavailability, and targeting ability compared with those of <b>5b</b> alone. Furthermore, the <i>in vitro</i>/<i>in vivo</i> results revealed that <b>5b</b>/<b>HSA-5b</b> NPs could integrate chemotherapy and immunotherapy by synergistically attacking two different cellular components in TME at the same time, namely, polarizing the tumor-associated macrophages and inducing apoptosis of gastric cancer cells.