Abstract
Transarterial chemoembolization (TACE) has been extensively used in clinic to treat unresectable hepatocellular carcinoma (HCC). Herein, magnesium microspheres (Mg MSs) were used as embolic devices to enhance lipiodol-mediated TACE. After being dispersed in lipiodol and injected into tumors, Mg MSs would continuously generate hydrogen and magnesium hydroxide, which could neutralize the acidic tumor microenvironment, restore exhausted CD8+ T cells, reverse immunosuppression, and trigger specific T cell-mediated antitumor responses, synergistically resulting in inhibited tumor growth. As demonstrated in a rabbit orthotopic liver cancer model, artery infusion of Mg MS-dispersed lipiodol offered greatly enhanced therapeutic outcome compared to lipiodol-based or polymeric-bead-based TACE. In a pilot clinical study, among 15 eligible patients with HCC, 11 patients achieved complete response and 3 patients achieved partial responses without unexpected treatment-related adverse events during the 1 to 3 months' follow-up. The objective response rate of Mg-enhanced TACE was ~93.3% in this small-scale trial, much higher than that of current TACE therapies.