Zein‐Based Triple‐Drug Nanoparticles to Promote Anti‐Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy‐promoting, anti‐inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are co...

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Bibliographic Details
Published in:Advanced healthcare materials 2024-07, Vol.13 (18), p.e2304261-n/a
Main Authors: Wang, Jingxuan, Lin, Yan, Li, Chunhan, Lei, Fei, Luo, Hongli, Jing, Pei, Fu, Yao, Zhang, Zhirong, Wang, Changguang, Liu, Zerong, Jiang, Jun, Zhou, Meiling, Du, Xingjie, Liu, Zhongbing, Zhou, Xiangyu, Sun, Xiaoduan, Zhong, Zhirong
Format: Article
Language:English
Subjects:
Autophagy
Biocompatibility
Cell culture
Drugs
everolimus
Hydrogen peroxide
Inflammation
Lipopolysaccharides
Metformin
Microglia
Nanoparticles
Nerves
Neurological diseases
Regeneration
Spinal cord injuries
spinal cord injury
TOR protein
Toxicity
Zein
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Summary:Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy‐promoting, anti‐inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein‐based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH‐SY5Y neuron‐like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH‐SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple‐drug nanoparticles show promise for treating spinal cord injury. The authors developed a nanosystem, the metformin‐ and everolimus‐loaded nanoparticles (Cel‐MET‐EVE@NPs), to deliver autophagy‐promoting anti‐inflammatory drugs to nerve cells and promote autophagy after spinal cord injury. Celastrol is incorporated into the surface of nanoparticles to synergistically promote autophagy and reduce inflammation. Cel‐MET‐EVE@NPs show promise for treating spinal cord injury.
ISSN:2192-2640
2192-2659
2192-2659
DOI:10.1002/adhm.202304261