Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma

Abstract This paper introduces catheter‐directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion‐crosslinked hyaluronic acid‐dopamine (HD) with glucose oxidase (for glucose decomposition to H₂O₂ in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X‐ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X‐ray fluoroscopy. Mn⁴⁺ (from MnO₂) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O₂ generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn²⁺. The gelation time‐controlled, catheter‐injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC‐bearing animal models. The developed radiopaque/injectable/embolic/sol‐to‐gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.