Advanced Microsphere and Hydrogel Platforms for Precision Interventional Therapy of Hepatocellular Carcinoma

ABSTRACT Interventional management of hepatocellular carcinoma (HCC) remains hindered by profound tumor heterogeneity and an immunosuppressive microenvironment. While transarterial chemoembolization (TACE) constitutes the current standard of care, its therapeutic efficacy is compromised by burst drug release, incomplete vascular occlusion, and systemic toxicity. Emerging advanced biomaterial platforms—microspheres and hydrogels—are redefining this paradigm by enabling precise spatial and temporal control over embolization and drug delivery. Microspheres provide hierarchical vascular occlusion and sustained release through tunable size and mechanical properties, addressing the limitations of conventional lipiodol formulations. Hydrogels offer exceptional injectability, high payload capacity, and conformal filling of irregular cavities, thereby facilitating controlled intratumoral release and microenvironment modulation. Beyond embolization, these systems integrate seamlessly with multimodal therapies—including magnetic hyperthermia, radiotherapy, and immunotherapy—delivering synergistic “embolization–therapy–diagnosis” functionality. Incorporation of stimuli‐responsive motifs, imaging agents, and immunomodulators further enables localized ablation, reversal of immunosuppression, and induction of systemic antitumor immunity to suppress metastasis and recurrence. Despite encouraging preclinical outcomes, clinical translation faces challenges in biocompatibility, scalable fabrication, and standardized evaluation. This review highlights design strategies for next‐generation embolic materials that integrate precision embolization, multimodal imaging, and immune reprogramming, thereby advancing interventional HCC therapy toward intelligent and personalized solutions.