Magnesium microspheres for enhanced transarterial chemoembolization therapy of hepatocellular carcinoma: From animal models to a pilot clinical study.

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 CD8T 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.