Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin 150001, China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China.
Nano Lett. 2022 Aug 10;22(15):6409-6417. doi: 10.1021/acs.nanolett.2c02472. Epub 2022 Jul 22.
The development of a manageable reactive nitrogen species-potentiated nitrosative stress induction system for cancer therapy has remained elusive. Herein, tailored silica-based nanoscintillators were reported for low-dosage X-ray boosting for the in situ formation of highly cytotoxic peroxynitrite (ONOO). Significantly, cellular nitrosative stress revolving around the intracellular protein tyrosine nitration through ONOO pathways was explored. High-energy X-rays were directly deposited on silica-based nanoscintillators, forming the concept of an open source and a reduced expenditure-aggravated DNA damage strategy. Moreover, the resultant ONOO, along with the released nitric oxide, not only can act as "oxygen suppliers" to combat tumor hypoxia but also can induce mitochondrial damage to initiate caspase-mediated apoptosis, further improving the therapeutic efficacy of radiotherapy. Thus, the design of advanced nanoscintillators with specific enhanced nitrosative stress offers promising potential for postoperative radiotherapy of colon cancer.
开发一种可控的活性氮物种增强的硝化应激诱导系统用于癌症治疗一直难以实现。本文报道了一种定制的基于二氧化硅的纳米闪烁体，用于低剂量 X 射线增强，以原位形成高细胞毒性过氧亚硝酸盐（ONOO）。重要的是，通过 ONOO 途径探讨了围绕细胞内酪氨酸蛋白硝化的细胞硝化应激。高能 X 射线直接沉积在基于二氧化硅的纳米闪烁体上，形成了开源和降低支出加剧 DNA 损伤策略的概念。此外，所产生的 ONOO 与释放的一氧化氮不仅可以作为“氧气供应源”来对抗肿瘤缺氧，还可以诱导线粒体损伤引发半胱天冬酶介导的细胞凋亡，从而进一步提高放射治疗的疗效。因此，设计具有特定增强硝化应激的先进纳米闪烁体为结肠癌术后放疗提供了有前途的潜力。
