Lipoic Acid/Choline Ionic Liquid Enhanced Intratumoral Heat/Mass Transfer for Suppressing Thermo-Mediated Tumor Relapse and Metastasis

Abstract

Thermal ablation (TA) is widely used for clinical treatment of various cancers. However, TA often struggles to efficiently kill tumor cells without injuring adjacent normal tissues/cells, leading to thermo-mediated tumor relapse and metastasis, owing to the immunosuppressive microenvironment surrounding residual tumor cells. In this study, a temperature-sensitive ionic liquid composed of lipoic acid and choline (LACH/PNA) is developed as a multifunctional TA sensitizer to suppress tumor metastasis induced by incomplete microwave ablation. LACH/PNA exhibits a high diffusion coefficient by disrupting the tumor matrix and modulating cancer-associated fibroblasts, thereby facilitating heat and mass transfer in tumors. LACH/PNA demonstrates greater cytotoxicity toward hepatoma cells than on normal hepatocytes with this effect further intensified by thermal treatment. These findings highlight LACH/PNA as a promising multifunctional sensitizer for clinical chemoablation-microwave ablation synergy.