Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Material Science, Hebei University, Baoding 071002, China.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Material Science, Hebei University, Baoding 071002, China.
J Colloid Interface Sci. 2024 Jan 15;654(Pt A):774-784. doi: 10.1016/j.jcis.2023.10.092. Epub 2023 Oct 19.
Chemodynamic therapy (CDT) based on hydroxyl radicals (•OH) to suppress tumor cells is a promising strategy due to its efficacy and safety. Nevertheless, in tumor cells, CDT still faces challenges such as insufficient •OH and weak killing effect of tumor cells under physiological conditions due to inadequate amounts of endogenous hydrogen peroxide (HO) and heightened glutathione expression. These challenges limit the therapeutic potential of CDT. To improve the effects of CDT, combination treatment strategies have been developed. Here, we report a rationally designed nanocomposite (CaO@Cu-LA) with self-supplying HO ability from calcium peroxide, and nitric oxide (NO) generation ability from l-arginine. NO molecules not only exhibit a strong killing effect, but also have the potential to transfer into the more cytotoxic substance peroxynitrite anion by reacting with reactive oxygen species. The results showed that CaO@Cu-LA could significantly suppress tumor growth by increasing •OH radicals and NO molecules. Taken together, the strategy developed here provides a good application foreground to yield a remarkable synergistic antitumor effect of CDT and NO gas therapy.
基于羟自由基（•OH）抑制肿瘤细胞的化学动力学疗法（CDT）因其疗效和安全性而备受关注。然而，在肿瘤细胞中，由于内源性过氧化氢（HO）含量不足和谷胱甘肽表达水平升高，CDT 仍然面临着诸如•OH 不足和生理条件下肿瘤细胞杀伤效果较弱等挑战。这些挑战限制了 CDT 的治疗潜力。为了提高 CDT 的效果，已经开发了联合治疗策略。在这里，我们报告了一种合理设计的纳米复合材料（CaO@Cu-LA），它具有过氧化钙自供 HO 的能力，以及 L-精氨酸产生 NO 的能力。NO 分子不仅具有很强的杀伤作用，而且通过与活性氧反应还有可能转化为更具细胞毒性的过氧亚硝酸盐阴离子。结果表明，CaO@Cu-LA 可以通过增加•OH 自由基和 NO 分子来显著抑制肿瘤生长。综上所述，该研究中开发的策略为提高 CDT 和 NO 气体治疗的协同抗肿瘤效果提供了良好的应用前景。
