Dual-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis

Abstract

Hepatocellular carcinoma (HCC) is a major public health threat due to its high incidence and mortality rates. Transcatheter arterial chemoembolization (TACE), the primary treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), commonly utilizes embolic agents loaded with anthracycline-based cytotoxic drugs. Post-TACE, the hypoxic microenvironment in the tumor induced by embolization stimulates the formation of new blood vessels, potentially leading to revascularization and diminishing TACE's efficacy. In clinical practice, combined therapy for liver cancer using TACE and oral targeted drugs often encounters the limitation that targeted drugs cannot efficiently reach the tumor site following TACE. We have developed chondroitin sulfate microspheres (CMs) capable of encapsulating both the cytotoxic drug idarubicin (Ida) and the vascular inhibitor Lenvatinib (Len), thereby achieving a triple therapeutic effect on liver cancer: embolic starvation, drug toxicity, and efficient inhibition of neovascularization.