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

Area of Science:

• Nanomedicine
• Cancer Therapy
• Materials Science

Background:

• Gastric cancer treatment remains challenging, necessitating innovative therapeutic strategies.
• The tumor microenvironment (TME) presents complex barriers to effective drug delivery and treatment efficacy.
• Integrating chemotherapy and immunotherapy offers a promising approach to overcome treatment resistance.

Purpose of the Study:

• To develop a novel metal-based agent for dual-targeting the TME in gastric cancer.
• To create a human serum albumin nanoparticle (HSA-NP) delivery system for enhanced therapeutic outcomes.
• To investigate the combined chemotherapy and immunotherapy potential of the developed agent and delivery system.

Main Methods:

• Synthesis of gold(III) α-N-heterocyclic thiosemicarbazone compounds, identifying agent 5b.
• Construction of a novel HSA-NP delivery system complexed with the gold agent (HSA-5b).
• In vitro and in vivo evaluation of cytotoxicity, tumor growth inhibition, and therapeutic efficiency.

Main Results:

• The gold agent 5b demonstrated significant cytotoxicity against gastric cancer cells.
• HSA-5b NPs effectively inhibited gastric tumor growth in vivo.
• HSA-5b NPs improved therapeutic efficiency, bioavailability, and targeting ability compared to the agent alone.
• The NPs synergistically polarized tumor-associated macrophages and induced gastric cancer cell apoptosis, integrating chemotherapy and immunotherapy.

Conclusions:

• The developed HSA-5b NPs represent a promising nanomedicine platform for gastric cancer treatment.
• This dual-targeting strategy effectively combines chemotherapy and immunotherapy by modulating the TME.
• The enhanced bioavailability and targeting of HSA-5b NPs offer improved therapeutic potential over the free agent.