声音免疫疗法具有抑制深部肿瘤的巨大潜力；然而，同时消除“domestic”肿瘤细胞并调节“community”肿瘤免疫微环境的智能声音疗法药剂很少被开发。在此，我们报告了一种具有时空可控性的半导体铁螯合纳米金属调节剂（SINM）用于癌症的高敏声音金属免疫疗法。SINM由半导体聚合物（SP）骨架和噻吩类席夫碱结构螯合铁离子（Fe3+）的部分以及亲水侧链组成。在体内系统给药后，SINM在肿瘤中特异性地引发铁死亡和M1巨噬细胞极化，因其对肿瘤氧化还原环境的响应；同时，Fe3+的螯合增强了SP的声敏化效应，导致产生更多的活性氧物质以促进免疫细胞凋亡。这种SINM的声免疫金属疗法能够有效消除深层肿瘤并对免疫表型进行时空调节。 ©2023 Wiley-VCH GmbH.

Sono-immunotherapy holds great potential for deep tumor inhibition; however, smart sono-therapeutic agents to simultaneously eliminate 'domestic' tumor cells and regulate the 'community' tumor immune microenvironment have rarely been developed. Herein, we report a spatiotemporally controllable semiconducting iron-chelated nano-metallomodulator (SINM) for hypersensitive sono-metallo-immunotherapy of cancer. SINM consists of a semiconducting polymer (SP) backbone chelating iron ions (Fe3+) with thiophene-based Schiff base structure, and a hydrophilic side chain. Upon accumulation in tumor after systemic administration, SINM specifically arouses ferroptosis and M1 macrophage polarization due to its response toward the tumor redox environment; meanwhile, the chelation of Fe3+ enhances the sono-sensitizing effect of SPs, leading to enhanced generation of reactive oxygen species for immunogenic cell death. Such combined sonodynamic metallo-immunotherapy of SINM efficiently ablates deep tumor and spatiotemporally regulates immunophenotypes.© 2023 Wiley-VCH GmbH.