期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 31, 页码 37746-37760出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c12675
关键词
natural product; blood-brain barrier; noninvasive targeted delivery; neuronal mitochondria; neurodegenerative disease
资金
- Guangdong Basic and Applied Basic Research Foundation [2019B1515120043]
- Research Fund of University of Macau [MYRG2019-00121-ICMS, MYRG2018-00207-ICMS]
- Science and Technology Development Fund, Macau SAR [0098/2020/A]
- Guangdong Basic and Applied Basic Research Foundation for Distinguished Young Scholars [2020B1515020027]
- Guangzhou Science and Technology Bureau [202002020070, 202102010181, 202102010007]
- key Project of Basic Research of Shenzhen [JCYJ20200109113603854]
The study demonstrates that the ZIF-8@PB-QCT nanocomposite can effectively penetrate the BBB and treat Parkinson's disease by increasing ATP levels, reducing oxidative stress, and reversing neuronal damage through the activation of the PI3K/Akt signaling pathway. Additionally, the nanocomposite shows promise as a treatment for neurodegenerative diseases when combined with noninvasive NIR radiation.
Mitochondrial dysfunction, which is directly involved in Parkinson's disease (PD), is characterized by the production of reactive oxygen species (ROS) and aberrant energy metabolism. Thus, regulating mitochondrial function might be an effective strategy to treat PD. However, the blood-brain barrier (BBB) presents a significant challenge for the intracerebral delivery of drugs. Here, we synthesized a zeolitic imidazolate framework 8coated Prussian blue nanocomposite (ZIF-8@PB), which was encapsulated with quercetin (QCT), a natural antioxidant, to treat PD. ZIF-8@PB-QCT exhibited superior near-infrared radiation (NIR) response and penetrated through the BBB to the site of mitochondrial damage guided by the photothermal effect. In the mice model of PD, the QCT released from ZIF-8@PB-QCT significantly increased the adenosine triphosphate levels, reduced the oxidative stress levels, and reversed dopaminergic neuronal damage as well as PD-related behavioral deficits without any damage to the normal tissues. Furthermore, we explored the underlying neuroprotective mechanism of ZIF-8@PB-QCT that was mediated by activating the PI3K/Akt signaling pathway. Thus, combined with noninvasive NIR radiation, the biocompatible ZIF-8@PB-QCT nanocomposite could be used to treat neurodegenerative diseases.
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