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 (5b) with remarkable cytotoxicity to gastric cancer cells; moreover, we successfully constructed a novel HSA-5b complex NP delivery system. Importantly, the in vivo results showed that 5b/HSA-5b NPs effectively inhibited gastric tumor growth and HSA-5b NPs enhanced the therapeutic efficiency, bioavailability, and targeting ability compared with those of 5b alone. Furthermore, the in vitro/in vivo results revealed that 5b/HSA-5b 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.

Metalloimmunotherapy with Rhodium and Ruthenium Complexes: Targeting Tumor‐Associated Macrophages

“…In particular, gold compounds have been studied for their immunogenic effects and effects on TAMs. Recent work with Au(III) complexes, [55] among others, [22c,56] exemplifies the utility of gold complexes towards TAMs. Unlike gold, rhodium and ruthenium complexes have yet to be tested on macrophages in settings that mimic the tumor microenvironment.…”

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…The results showed that 267e /HSA- 267e nanoparticles can simultaneously target two different cellular components in tumor microenvironment and integrate chemotherapy and immunotherapy to induce cancer cell apoptosis. 203 In 2021, Possato et al reported two Au( iii )–thiosemicarbazonate complexes 268 and 269 and studied their antiproliferative activity. 268 exhibited better cytotoxicity than complex 269 .…”

Recent Advancement in Biological Sciences

“…5. Immunotherapy: By this process, medicine encourages the body's immune cells to attack cancer affected cells (Matsueda & Graham, 2014;Zhang et al, 2021a). This therapy is used when a candidate has received two or more other treatments (Dolcetti & De, 2019).…”