Mannose-coated superparamagnetic iron oxide nanozyme for preventing postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is associated with increased postoperative morbidity and mortality in patients. Excessive production of reactive oxygen species (ROS) and the consequent inflammatory response in the postoperative brain play crucial roles in the development of POCD. However, effective ways to prevent POCD have yet to be developed. Moreover, effective penetration of the blood-brain barrier (BBB) and maintaining viability in vivo are major challenges for preventing POCD using traditional ROS scavengers. Herein, mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized by co-precipitation method. The BBB penetration of mSPIONs was verified through fluorescent imaging and ICP-MS quantification. The ROS scavenging and anti-inflammatory of mSPIONs were evaluated in H2O2-treated J774A.1 cells and in tibial fracture mice model. The novel object recognition (NOR) and trace-fear conditioning (TFC) were used to test the cognitive function of postoperative mice. The average diameter of mSPIONs was approximately 11 nm. mSPIONs signifi-cantly reduced ROS levels in H2O2-treated cells and in hippocampus of surgical mice. mSPIONs administration reduced the levels of IL-1 beta and TNF-alpha in the hippocampus and inhibited surgery-upregulated HIF1-alpha/NF-kappa B signaling pathway. Moreover, mSPIONs significantly improved the cognitive function of postoperative mice. This study provides a new approach for preventing POCD using a nanozyme.

Automated summary

Postoperative cognitive dysfunction (POCD) is a significant problem that can lead to increased morbidity and mortality in patients. The excessive production of reactive oxygen species (ROS) and inflammation in the brain after surgery are major contributors to the development of POCD. In this study, mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to effectively scavenge ROS and reduce inflammation, ultimately improving cognitive function in postoperative mice. These findings suggest that mSPIONs may be a promising strategy for preventing POCD.