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

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.