Top - down Nanoscavengers for the protection of organophosphate-challenged cells
Top - down Nanoscavengers for the protection of organophosphate-challenged cells
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DOI：
10.1016/j.giant.2023.100213
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发表时间：
2023-12-02
期刊：
影响因子：
7
通讯作者：
Zhang，Liming
中科院分区：
文献类型：
--
作者：
Zou，Shuaijun;Wang，Qianqian;Zhang，Liming
背景有机磷酸盐（OPs）可以直接毒害各种类型的哺乳动物细胞，只有几种尴尬的自下而上的拮抗剂。开发了一种自上而下的纳米清除剂，以从根本上从病因学角度防止细胞损伤，同时探索了不充分的亚细胞或分子阻断机制。方法首先开发了自上而下的纳米清除剂并仔细表征。然后采用EL4细胞作为模型细胞来阐明纳米清除剂的保护作用和机制。在检测细胞活力和凋亡、氧化应激和线粒体损伤标志物、DNA损伤指数以及相关凋亡因子后，依次检测自上而下的纳米清道夫抑制的损伤。结果充分表征的纳米清道夫通过从根本上消除OPs和阻断，对EL4细胞活力发挥自上而下和病因学的保护作用 OP-细胞相互作用。结果，细胞内氧化应激相关标志物，包括ROS产生和异常抗氧化剂、线粒体损伤以及DNA损伤都受到抑制。因此，上述损伤诱导的细胞凋亡也被阻断。结论总而言之，本研究阐明了新型酶基纳米清除剂对OP攻击细胞的保护机制，并为OP中毒提供了一种有效的解毒剂。
BackgroundOrganophosphates (OPs) can directly poison various types of mammalian cells, only with several awkward bottom-up antagonists. A top-down nanoscavenger was developed to radically and etiologically prevent cell damage, while insufficient subcellular or molecular blocking mechanisms were explored.MethodsThe top-down nanoscavengers were first developed and carefully characterized. EL4 cells were then adopted as model cells to clarify the protective effects and mechanisms of nanoscavengers. After detecting the cell viability and apoptosis, oxidative stress and mitochondrial injury markers, DNA damage index as well as relevant apoptotic factors were sequentially examined to clarify what damage the top-down nanoscavengers inhibited.ResultsThe well-characterized nanoscavengers exerted a top-down and etiological protective effects on EL4 cell viability via radically eliminating OPs and blocking OP-cell interactions. As a result, the intracellular oxidative stress-related markers including ROS production and abnormal antioxidants, mitochondrial injuries as well as DNA damage were inhibited. Accordingly, above damage-induced apoptosis was also blocked.ConclusionIn conclusion, this study clarified the protective mechanisms of a novel enzyme-based nanoscavengers for OP-challenged cells and provided a potent antidote for OP poisoning.