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Yu Hu,1– 3 Hui Guo,1– 3 Shuai Cheng,1– 3 Junpeng Sun,2,4 Jiaqun Du,2,4 Xiaobang Liu,2,4 Ying Xiong,5 Liqing Chen,6 Chang Liu,3,6 Chao Wu,2,4 He Tian1– 3 1School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 2Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 3Key Laboratory of Medical Tissue Engineering of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 4Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 5Laboratoire Catalyse et Spectrochimie (LCS), Normandie Université, ENSICAEN, UNICAEN, CNRS, Caen, 14050, France; 6Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People’s Republic of ChinaCorrespondence: He Tian; Chao Wu, Email tianhe@jzmu.edu.cn; wuchao@jzmu.edu.cnBackground: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid β (Aβ) in the nervous system are significant contributors to Alzheimer’s disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection.Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis.Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aβ-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aβ-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration.Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aβ aggregation, and promote the recovery of neurological function.Keywords: cerium dioxide nanoparticles, manganese, oxidative stress, resveratrol, Alzheimer’s disease |
