Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, China.
ACS Biomater Sci Eng. 2021 Apr 12;7(4):1394-1402. doi: 10.1021/acsbiomaterials.0c01678. Epub 2021 Mar 9.
Chemodynamic therapy (CDT) is a kind of method utilizing hydroxyl radicals (OH) generated by Fenton or Fenton-like reactions to kill tumor cells. Copper, a cofactor of many intracellular enzymes, which has good biocompatibility, is a transition metal with extremely high efficiency in the Fenton-like reaction. However, when the intracellular free copper exceeds the threshold, it will bring serious side effects. Hence, we used the chelation between glutathione (GSH) and copper ions to produce a nanocatalytic drug, which was named as Cu-GSSG NPs, to fix free copper. With the aid of hydrogen peroxide (HO) , Cu-GSSG NPs catalyzed it to OH radicals, which could be confirmed by the electron spin resonance spectrum and the degradation experiment of methylene blue. Based on these results, we further studied the intracellular properties of Cu-GSSG NPs and found that Cu-GSSG NPs could react with the overexpressed HO in tumor cells to produce OH radicals effectively by the Fenton-like reaction to induce cell death. Therefore, Cu-GSSG NPs could be a kind of potential "green" nanocatalytic drug with good biocompatibility to achieve CDT.
化学动力学治疗(CDT)是一种利用芬顿或类芬顿反应产生的羟基自由基(OH)来杀死肿瘤细胞的方法。铜是许多细胞内酶的辅因子,具有良好的生物相容性,是一种在类芬顿反应中具有极高效率的过渡金属。然而,当细胞内游离铜超过阈值时,会带来严重的副作用。因此,我们利用谷胱甘肽(GSH)与铜离子的螯合作用,制备了一种纳米催化药物,命名为 Cu-GSSG NPs,以固定游离铜。在过氧化氢(HO)的辅助下,Cu-GSSG NPs 可以催化其产生 OH 自由基,这可以通过电子自旋共振谱和亚甲基蓝的降解实验来证实。基于这些结果,我们进一步研究了 Cu-GSSG NPs 的细胞内性质,发现 Cu-GSSG NPs 可以通过类芬顿反应与肿瘤细胞中过表达的 HO 有效反应,产生 OH 自由基,从而诱导细胞死亡。因此,Cu-GSSG NPs 可以成为一种具有良好生物相容性的潜在“绿色”纳米催化药物,以实现 CDT。