Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease
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 In...
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Dove Medical Press
2023-11-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/functionalized-cerium-dioxide-nanoparticles-with-antioxidative-neuropr-peer-reviewed-fulltext-article-IJN |
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| author | Hu Y Guo H Cheng S Sun J Du J Liu X Xiong Y Chen L Liu C Wu C Tian H |
| author_facet | Hu Y Guo H Cheng S Sun J Du J Liu X Xiong Y Chen L Liu C Wu C Tian H |
| author_sort | Hu Y |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-11T09:40:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-11T09:40:17Z |
| publishDate | 2023-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-d60884a6c4af4edfbd300617aa03473d2023-11-16T17:04:56ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-11-01Volume 186797681288266Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s DiseaseHu YGuo HCheng SSun JDu JLiu XXiong YChen LLiu CWu CTian HYu 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 diseasehttps://www.dovepress.com/functionalized-cerium-dioxide-nanoparticles-with-antioxidative-neuropr-peer-reviewed-fulltext-article-IJNcerium dioxide nanoparticlesmanganeseoxidative stressresveratrolalzheimer's disease |
| spellingShingle | Hu Y Guo H Cheng S Sun J Du J Liu X Xiong Y Chen L Liu C Wu C Tian H Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease International Journal of Nanomedicine cerium dioxide nanoparticles manganese oxidative stress resveratrol alzheimer's disease |
| title | Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease |
| title_full | Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease |
| title_fullStr | Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease |
| title_full_unstemmed | Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease |
| title_short | Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer’s Disease |
| title_sort | functionalized cerium dioxide nanoparticles with antioxidative neuroprotection for alzheimer rsquo s disease |
| topic | cerium dioxide nanoparticles manganese oxidative stress resveratrol alzheimer's disease |
| url | https://www.dovepress.com/functionalized-cerium-dioxide-nanoparticles-with-antioxidative-neuropr-peer-reviewed-fulltext-article-IJN |
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