鉴于肿瘤微环境（TME）对治疗反应和临床结果产生不利影响，强大的TME调节剂可能会显着提高癌症患者的疗效并增加生存获益。在这里，开发了带有聚乙二醇化的金纳米点锚定 CoFe2O4 纳米花（CFAP）来响应 TME 信号，旨在加剧氧化还原失调，从而在超声（US）照射下进行有效的抗肿瘤治疗。被肿瘤细胞摄取后，具有葡萄糖氧化酶（GOx）样活性的CFAP可以促进葡萄糖消耗并促进H2O2的产生。 CFAP 中的 Co(II)/Co(III) 和 Fe(II)/Fe(III) 多价元素对 H2O2 生成·OH 表现出强芬顿样活性。另一方面，能带结构 CFAP 依赖于 e-/h 对的增强分离和延迟复合，对于 US 驱动的 1O2 生成更为优越。此外，模拟过氧化氢酶的CFAP可以与胞质H2O2反应产生分子氧，这可能会增加耗氧反应（例如葡萄糖氧化和声敏过程）的产物产量。除了大量产生活性氧外，CFAP 还能够耗尽谷胱甘肽，破坏细胞内的氧化还原平衡。 CFAP 的严重免疫原性细胞死亡和对实体瘤的有效抑制证明了这种异质结构的临床效力，并可能激发更多相关的疾病治疗设计。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

Given that tumor microenvironment (TME) exerts adverse impact on the therapeutic response and clinical outcome, robust TME modulators may significantly improve the curative effect and increase survival benefits of cancer patients. Here, Au nanodots-anchored CoFe2O4 nanoflowers with PEGylation (CFAP) are developed to respond to TME cues, aiming to exacerbate redox dyshomeostasis for efficacious antineoplastic therapy under ultrasound (US) irradiation. After uptake by tumor cells, CFAP with glucose oxidase (GOx)-like activity can facilitate glucose depletion and promote the production of H2O2. Multivalent elements of Co(II)/Co(III) and Fe(II)/Fe(III) in CFAP display strong Fenton-like activity for·OH production from H2O2. On the other hand, energy band structure CFAP is superior for US-actuated 1O2 generation, relying on the enhanced separation and retarded recombination of e-/h+ pairs. In addition, catalase-mimic CFAP can react with cytosolic H2O2 to generate molecular oxygen, which may increase the product yields from O2-consuming reactions, such as glucose oxidation and sonosensitization processes. Besides the massive production of reactive oxygen species, CFAP is also capable of exhausting glutathione to devastate intracellular redox balance. Severe immunogenic cell death and effective inhibition of solid tumor by CFAP demonstrates the clinical potency of such heterogeneous structure and may inspire more relevant designs for disease therapy.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.