恶性肿瘤对人类健康构成严重威胁。抗坏血酸（AA）具有治疗肿瘤的潜力；然而，AA 选择性杀死肿瘤细胞的能力的机制仍不清楚。 AA可引起肿瘤细胞氧化还原不平衡，导致释放大量以过氧化氢（H2 O2）为代表的活性氧。因此，检测H2O2的变化可以深入了解AA对肿瘤细胞的选择性杀伤机制。在这项工作中，受珊瑚形成中离子交换机制的启发，构建了一种柔性H2O2传感器（PtNFs/CoPi@CC）来监测细胞微环境中H2O2的动态，该传感器表现出优异的灵敏度和时空分辨率。此外，研究结果表明，AA 的氧化产物脱氢抗坏血酸 (DHA) 很可能是 AA 疗法中真正作用于肿瘤细胞的物质。此外，DHA引起的细胞内氧化还原不平衡和H2O2释放与葡萄糖转运蛋白1（GLUT1）的丰度和活性呈正相关。总之，这项工作揭示了 AA 通过构建和使用 PtNFs/CoPi@CC 选择性杀死肿瘤细胞的潜在机制。这些发现为 AA 的临床应用提供了新的见解。© 2023 作者。 《先进科学》由 Wiley-VCH GmbH 出版。

Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to selectively kill tumor cells remains unclear. AA can cause redox disequilibrium in tumor cells, resulting in the release of abundant reactive oxygen species, represented by hydrogen peroxide (H2 O2 ). Therefore, the detection of H2 O2 changes can provide insight into the selective killing mechanism of AA against tumor cells. In this work, inspired by the ion-exchange mechanism in coral formation, a flexible H2 O2 sensor (PtNFs/CoPi@CC) is constructed to monitor the dynamics of H2 O2 in the cell microenvironment, which exhibits excellent sensitivity and spatiotemporal resolution. Moreover, the findings suggest that dehydroascorbic acid (DHA), the oxidation product of AA, is highly possible the substance that actually acts on tumor cells in AA therapy. Additionally, the intracellular redox disequilibrium and H2 O2 release caused by DHA are positively correlated with the abundance and activity of glucose transporter 1 (GLUT1). In conclusion, this work has revealed the potential mechanism underlying the ability of AA to selectively kill tumor cells through the construction and use of PtNFs/CoPi@CC. The findings provide new insights into the clinical application of AA.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.