Institute of Molecular Science, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, China.
Institute of Molecular Science, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2024 Sep 5;317:124446. doi: 10.1016/j.saa.2024.124446. Epub 2024 May 10.
Developing the efficient nanozymes for reactive oxygen species (ROS)-mediated highly potent tumor catalytic therapy has become a great challenge. In this study, we prepared the DNA-Fe, -FeAg, and -FeCuAg nanocluster (NCs) using the G-/C-rich single-stranded DNA (ssDNA) templates. The steady-state kinetic and the catalytic performances and mechanisms of DNA-metal NCs were first systematically investigated. The results indicated that c-kit-TBA-Fe, c-kit-TBA-FeAg, and c-kit-TBA-FeCuAg NCs exhibited the high peroxidase-like activity. All of three types of NCs presented the higher affinity to the substrate TMB and better storage stability at 4 °C than horseradish peroxidase (HRP). Moreover, c-kit-TBA-FeAg and c-kit-TBA-FeCuAg NCs presented the 6.7- and 4.7-fold stronger affinity to TMB than c-kit-TBA-Fe, respectively. However, the maximum reaction rate (V) of c-kit-TBA-FeCuAg NCs with HO was the largest, which promoted the generation of much more OH in the reaction system. More importantly, c-kit-TBA-FeCuAg NCs were able to deplete largely the intracellular GSH and thus generate lots of endogenous ROS in HeLa cells, thereby exhibiting the significant and specific in vitro cancer cells toxicity. Therefore, c-kit-TBA-FeCuAg NCs, with peroxidase-like activity and glutathione (GSH) consumption ability, hold the ROS-based promising therapeutic effects for cancer.
开发用于活性氧（ROS）介导的高效肿瘤催化治疗的高效纳米酶已成为一项巨大的挑战。在本研究中，我们使用 G-/C-富含的单链 DNA（ssDNA）模板制备了 DNA-Fe、-FeAg 和 -FeCuAg 纳米团簇（NCs）。首次系统研究了 DNA-金属 NCs 的稳态动力学、催化性能和机制。结果表明，c-kit-TBA-Fe、c-kit-TBA-FeAg 和 c-kit-TBA-FeCuAg NCs 表现出高过氧化物酶样活性。这三种类型的 NCs 均对底物 TMB 具有更高的亲和力，在 4°C 下的储存稳定性也优于辣根过氧化物酶（HRP）。此外，c-kit-TBA-FeAg 和 c-kit-TBA-FeCuAg NCs 对 TMB 的亲和力分别比 c-kit-TBA-Fe 强 6.7 倍和 4.7 倍。然而，c-kit-TBA-FeCuAg NCs 与 HO 的最大反应速率（V）最大，这促进了反应体系中产生更多的 OH。更重要的是，c-kit-TBA-FeCuAg NCs 能够大量消耗细胞内的 GSH，从而在 HeLa 细胞中产生大量内源性 ROS，从而表现出显著的、特异性的体外癌细胞毒性。因此，具有过氧化物酶样活性和谷胱甘肽（GSH）消耗能力的 c-kit-TBA-FeCuAg NCs 具有基于 ROS 的有前途的癌症治疗效果。
