MOF-Mediated Aloe-Emodin Delivery Enhances Hepatocellular Carcinoma Immunotherapy via Pyroptosis and Immunosuppressant Synergy.

[PURPOSE] Hepatocellular carcinoma (HCC) remains a major global oncological burden, with conventional therapies showing limited efficacy. This study aimed to utilize pyroptosis to alleviate the tumor's immunosuppressive microenvironment, enhance systemic immunity, and improve immunotherapy efficacy, focusing on precise selection of pyroptosis inducers, immunotherapeutic agents, and drug delivery strategies.

[METHODS] After synthesizing AE-FeMn/FA, its morphology, particle size, and Zeta potential were characterized. We evaluated its catalytic performance in activating HO to produce ·OH, ability to trigger cellular pyroptosis, and in vitro/in vivo anti-tumor effects. Combined with BMS-202, we explored suppression of the PD-1/PD-L1 complex and synergistic induction of pyroptosis.

[RESULTS] Intravenous AE-FeMn/FA targeted HCC, with controlled AE release triggering pyroptosis and anti-tumor immunity. BMS-202 alleviated immunosuppression, enhancing AE-FeMn/FA-induced anti-tumor responses, achieving synergistic immune-mediated cancer cell elimination.

[CONCLUSION] The synergistic approach of pyroptosis combined with an enhanced immunotherapy nanoplatform shows promise as an effective HCC immunotherapy strategy, with significant clinical translation potential. Future studies will optimize the platform and conduct clinical trials.