声动力疗法受益于其卓越的时空选择性和非侵入性，可以触发免疫原性细胞死亡以增强免疫治疗。然而，声敏剂的实际应用因其杀死癌细胞和激活免疫反应的功效较低而受到阻碍。在这里，选择两种美国食品和药物管理局批准的药物配体（铁氰化物和硝普钠）和两种类型的金属（铜/铁）来构建双金属双配体框架（Cu[PBA-NO]）。通过对多种金属/配体配位的精心调控，全身给药的Cu[PBA-NO]纳米剂在超声照射下表现出声催化和NO释放能力，可用于有效的声免疫治疗。此外，Cu[PBA-NO] 可以下调细胞内谷胱甘肽水平，从而破坏细胞内氧化还原稳态并促进活性氧的积累。释放的肿瘤相关抗原随后促进肿瘤引流淋巴结内的树突状细胞成熟，有效启动T细胞介导的免疫反应，从而增强识别和对抗癌细胞的能力。这项研究为有效的癌症声免疫治疗开辟了一条新途径。© 2024 Wiley‐VCH GmbH。

Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.© 2024 Wiley‐VCH GmbH.