Intelligently thermoresponsive flower-like hollow nano-ruthenium system for sustained release of nerve growth factor to inhibit hyperphosphorylation of tau and neuronal damage for the treatment of Alzheimer's disease
| Autor: | Li Zhang, Ji-an Wei, Jie Liu, Xufeng Zhu, Jiawei Liu, Youcong Gong, Anlian Huang, Hui Zhou, Guanglong Yuan, Yanan Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Amyloid beta
Tau protein Biophysics Hyperphosphorylation tau Proteins Bioengineering 02 engineering and technology medicine.disease_cause Ruthenium Biomaterials Mice 03 medical and health sciences Alzheimer Disease Nerve Growth Factor medicine Animals Phosphorylation 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Amyloid beta-Peptides biology Chemistry Nerve injury 021001 nanoscience & nanotechnology medicine.disease Cell biology Nerve growth factor Mechanics of Materials Delayed-Action Preparations Ceramics and Composites biology.protein Tauopathy medicine.symptom 0210 nano-technology Oxidative stress |
| Zdroj: | Biomaterials. 237:119822 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2020.119822 |
| Popis: | Alzheimer's disease (AD) seriously affects human health and life and lacks effective treatments. The lessons of many clinical trial failures suggest that targeting amyloid beta to treat AD is difficult, and finding new targets is an important direction for AD drug research. The neurofibrillary tangles formed by hyperphosphorylation of tau protein induce the production of cytotoxic reactive oxygen species (ROS) and cause neuronal apoptosis. Therefore, inhibition of hyperphosphorylation of tau protein and reduction of neuronal damage have become promising methods for the treatment of AD. We herein designed a novel nanocomposite with high stability and good biocompatibility by using flower-shaped hollow nano-ruthenium (Ru NPs) as a carrier, loading nerve growth factor (NGF) and sealing with phase change material (PCM). Due to its excellent photothermal effect, under the near-infrared (NIR) irradiation, the nanocomposite could effectively penetrate the blood-brain barrier (BBB) and respond to phase changes in the lesion area, releasing NGF, which inhibited tau hyperphosphorylation, reduced oxidative stress, and more importantly restored nerve damage and maintained neuronal morphology, thereby significantly improving learning and memory in AD mice. Thus, the experimental results indicate that multifunctional nanocomposites may be a promising drug in the treatment of AD. |
| Databáze: | OpenAIRE |
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