Dual-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis
Jinxin Huang, Rui Yang, Huan Long, Jie Kong, Guoqiang Shao, Fei Xiong
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. Scheme 1. (A). Mechanism diagram of Len protonation. (B). Mechanism diagram of co-delivery of idarubicin Ida and Len by CMs. (C). Schematic representation of TACE for the treatment of liver cancer. (D). Mechanism diagram of dual-drug TACE treatment for liver cancer using CMs co-delivering Ida and Len. The released Ida directly induces DNA damage in tumor cells, leading to the destruction of liver cancer cells, while Len inhibits VEGFR2, thereby preventing the formation of new blood vessels in emerging liver cancer lesions.