Idarubicin-loaded degradable hydrogel for TACE therapy enhances anti-tumor immunity in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence. Traditional TACE uses agents like oil-based drug emulsions and polyvinyl alcohol particles, which can permanently block blood vessels and increase tumor hypoxia. Additionally, TACE can suppress the immune system by reducing immune cell numbers and function, contributing to poor treatment outcomes. New approaches, like TACE using degradable starch microspheres and hydrogel-based materials, offer the potential to create different tumor environments that could improve both safety and efficacy. In our research, we developed a composite hydrogel (IF@Gel) made of Poloxamer-407 gel and Fe₃O₄ nanoparticles, loaded with idarubicin, to use as an embolic material for TACE in a rat model of orthotopic HCC. We observed promising therapeutic effects and investigated the impact on the tumor immune microenvironment, focusing on the role of immunogenic cell death (ICD). The composite hydrogel demonstrated excellent potential as an embolic material for TACE, and IF@Gel-based TACE demonstrated significant efficacy in rat HCC. Furthermore, our findings highlight the potential synergistic effects of ICD with anti-PD-L1 therapy, providing new insights into HCC treatment strategies. This study aims to provide improved treatment options for HCC and to deepen our understanding of the mechanisms of TACE and tumor environment regulation.