Hypoxia-specific metal-organic frameworks combined with lactate immunometabolism regulation augment anti-tumor immunity of HIFU

neutralizes intratumoral lactate, reprogramming tumor-associated macrophages from immunosuppressive M2 phenotype toward pro-inflammatory M1 phenotype. Furthermore, the co-release of calcium and manganese ions trigger pyroptosis via mitochondrial ion overload and activate calcium-dependent NFAT pathway of T cells. As a result, AMCMOFs elicit the strong immune response and successfully induce long-lasting immune memory, effectively inhibiting tumor recurrence and metastasis. Therefore, the developed MOFs-based nanoplatform can combine the utilization and regulation of TME, offering a compelling strategy for improving the prognosis of all surgical operations, including HIFU, in oncotherapy.