State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
Institute of Nano-Science and Technology, College of Physical Science and Technology, Central China Normal University, Wuhan 430079, P. R. China.
ACS Nano. 2024 Sep 17;18(37):25685-25694. doi: 10.1021/acsnano.4c07851. Epub 2024 Sep 2.
Phosphates within tumors function as key biomolecules, playing a significant role in sustaining the viability of tumors. To disturb the homeostasis of cancer cells, regulating phosphate within the organism proves to be an effective strategy. Herein, we report single-atom Ce-doped Pt hydrides (Ce/Pt-H) with high phosphatase-like activity for phosphate hydrolysis. The resultant Ce/Pt-H exhibits a 26.90- and 6.25-fold increase in phosphatase-like activity in comparison to Ce/Pt and Pt-H, respectively. Mechanism investigations elucidate that the Ce Lewis acid site facilitates the coordination with phosphate groups, while the surface hydrides enhance the electron density of Pt for promoting catalytic ability in HO cleavage and subsequent nucleophilic attack of hydroxyl groups. Finally, by leveraging its phosphatase-like activity, Ce/Pt-H can effectively regulate intracellular phosphates to disrupt redox homeostasis and amplify oxidative stress within cancer cells, ultimately leading to tumor apoptosis. This work provides fresh insights into noble-metal-based phosphatase mimics for inducing tumor apoptosis.
肿瘤中的磷酸盐作为关键生物分子，在维持肿瘤的生存能力方面发挥着重要作用。为了扰乱癌细胞的内环境平衡，调节机体内的磷酸盐成为一种有效的策略。在此，我们报告了具有高磷酸酶样活性的单原子 Ce 掺杂 Pt 氢化物（Ce/Pt-H），可用于磷酸盐水解。与 Ce/Pt 和 Pt-H 相比，所得的 Ce/Pt-H 的磷酸酶样活性分别提高了 26.90 倍和 6.25 倍。机理研究表明，Ce 路易斯酸位促进了与磷酸盐基团的配位，而表面氢化物增强了 Pt 的电子密度，从而促进了 HO 裂解和随后的羟基亲核攻击中的催化能力。最后，通过利用其磷酸酶样活性，Ce/Pt-H 可以有效地调节细胞内磷酸盐，破坏氧化还原内环境平衡并在癌细胞内放大氧化应激，最终导致肿瘤细胞凋亡。这项工作为诱导肿瘤细胞凋亡的基于贵金属的磷酸酶模拟物提供了新的见解。
