Suppressing hyperthermia-induced up-regulated PD-L1 with a Sunitinib loaded Fe-Cu MOF: Strengthening immunogenic cell death to sensitize anti-PD-L1 effect following microwave ablation of hepatocellular carcinoma.

Microwave ablation (MWA) therapy has gained prominence as an effective yet minimally invasive hyperthermic method for the treatment of hepatocellular carcinoma (HCC). The upregulation of programmed death ligand 1 (PD-L1) and insufficient antitumor immune response induced by thermal injury, however, substantially limit the long-term efficacy of MWA. Suppression of PD-L1 combined with reactive oxygen species (ROS)-enhanced immunogenic cell death (ICD) mediated antitumor immunity is anticipated to improve the MWA prognosis. In this study, a Sunitinib (SUN)-loaded Fe-Cu MOF was designed to prevent tumor recurrence following MWA. The released Sunitinib effectively inhibits PD-L1 expression, which is upregulated by MWA-induced hyperthermic injury. Moreover, the MWA-enhanced dynamic sensitization of Fe-Cu MOF increases ROS production, thereby promoting stronger ICD and enhancing the SUN anti-PD-L1 effect. The presence of Cu and Fe with T1/T2 MR imaging properties enables real-time image-guided monitoring of MWA. Notably, the Fe-Cu MOF@PEG@SUN nanocomposites effectively counteracted MWA-induced PD-L1 upregulation and amplified the extent of ICD post-MWA, thereby enhancing the SUN-mediated anti-PD-L1 immune response and promoting antitumor immunity. Hence, this study offers a promising strategy and theoretical foundation for the integration of diagnostic imaging with MWA-based therapy for HCC.