Top-down Nanoscavengers for the protection of organophosphate-challenged cells

Abstract

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.