Top-down Nanoscavengers for the protection of organophosphate-challenged cells
Shuaijun Zou,
Qianqian Wang,
Juxingsi Song,
Guoyan Liu,
Fuhai Zhang,
Jie Li,
Fan Wang,
Yanan Hu,
Yongfei Lv,
Dayuan Zhou,
Qian He,
Beilei Wang,
Liming Zhang
Affiliations
Shuaijun Zou
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China; Department of Marine Biological Injury and Dermatology, Naval Medical Centre, Naval Medical University, Shanghai 200052, China
Qianqian Wang
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Juxingsi Song
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Guoyan Liu
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Fuhai Zhang
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Jie Li
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Fan Wang
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Yanan Hu
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Yongfei Lv
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Dayuan Zhou
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China
Qian He
The Third Affiliated Hospital, Naval Medical University, Shanghai 200433, China; Corresponding authors.
Beilei Wang
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China; Corresponding authors.
Liming Zhang
Department of Marine Biomedicine and Polar Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200433, China; Corresponding authors.
Background: Organophosphates (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. Methods: The 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. Results: The 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. Conclusion: In 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.
