放大氧化应激破坏细胞内氧化还原稳态可以加速肿瘤细胞死亡。在这项工作中，制备了氧化应激放大器（PP@T）用于增强肿瘤氧化治疗，以减少肿瘤生长和转移。通过将MTH1抑制剂（TH588）嵌入PDA包被的卟啉金属有机骨架PCN-224中，成功构建了纳米放大器。孔内可控释放的TH588被证明可以通过阻止8-oxo-dG的水解来阻碍MTH1介导的损伤修复过程，从而放大氧化应激并加剧超声下PP@T声动力治疗引起的氧化DNA损伤辐照。此外，PP@T可以有效诱导免疫原性细胞死亡，从而引发全身抗肿瘤免疫反应。当与免疫检查点阻断联合给药时，PP@T不仅能阻止原发肿瘤的进展，而且在乳腺癌小鼠模型（包括原位和人工全身转移模型）中实现了明显的抗转移。此外，纳米平台还提供光声成像用于体内治疗指导。总之，通过放大氧化应激和活性氧敏化免疫治疗，这种图像引导的纳米系统显示出针对肿瘤细胞的高度特异性、有效的联合治疗的潜力，并且对正常细胞的副作用可以忽略不计，这将为肿瘤的精准治疗提供新的见解。 © 2024 作者。先进医疗保健材料由 Wiley‐VCH GmbH 出版。

Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano-amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA-coated porphyrin metal-organic framework PCN-224. The controllable-released TH588 is demonstrated from pores can hinder MTH1-mediated damage-repairing process by preventing the hydrolysis of 8-oxo-dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole-body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image-guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side-effects to normal cells which will provide a new insight for precise tumor treatment.© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.