Manganese-based metal-organic frameworks augment postoperative immunotherapy of high-intensity focused ultrasound

Limited antigen presentation renders high-intensity focused ultrasound (HIFU)-triggered immune response insufficient to improve prognosis. Herein, manganese-based metal-organic frameworks (termed AMS MOFs) were designed to co-deliver hypoxia-activated prodrug banoxantrone (AQ4N) and stimulator of interferon genes (STING) agonist SR-717, for enhancing antigen presentation-related postoperative immunotherapy. Under hypoxic microenvironment after HIFU surgery, the released AQ4N initiated immunogenic cell death causing the release of danger-associated molecular patterns. Simultaneously, SR-717 activated STING pathway and together with Mn²⁺-promoted the binding affinity of cGAMP-STING, finally eliciting robust type I interferon response. The synergism of these processes consequently promoted immune responses relevant to tumor antigen presentation and inhibited breast tumor recurrence and metastasis. This study presents a strategy for improving the overall prognosis of all surgery including HIFU.