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Ultrasound-Excited Protoporphyrin IX-Modified Multifunctional Nanoparticles as a Strong Inhibitor of Tau Phosphorylation and beta-Amyloid Aggregation.

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成果类型:
期刊论文
作者:
Xu, Mengmeng;Zhou, Hui;Liu, Yanan*;Sun, Jing;Xie, Wenjie;Zhao, Ping;Liu, Jie*
通讯作者:
Liu, Jie;Liu, Yanan
作者机构:
[Liu, Jie; Xu, Mengmeng; Sun, Jing; Zhou, Hui; Liu, Yanan; Xie, Wenjie] Department of Chemistry , Jinan University , Guangzhou 510632 , China
[Zhao, Ping] Department of Chemistry and Chemical Engineering , Guangdong Pharmaceutical University , Guangzhou 510006 , China
通讯机构:
[Liu, Jie; Liu, Yanan] Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China.
语种:
英文
关键词:
protoporphyrin IX;focused ultrasound;amyloid beta;phosphorylated tau;photothermal effect;multiple targets
期刊:
ACS APPLIED MATERIALS & INTERFACES
ISSN:
1944-8244
年:
2018
卷:
10
期:
39
页码:
32965-32980
文献类别:
WOS:Article
所属学科:
WOS学科类别:Materials Science, Multidisciplinary;Nanoscience & Nanotechnology
入藏号:
WOS:000446919800005;PMID:30192126
基金类别:
National Natural Science Foundation of China [21877051, 81803027, 21371075]; Natural Science Foundation of Guangdong Province [2014A030311025, 2018A030310628]; Planned Item of Science and Technology of Guangdong Province [2016A020217011]
机构署名:
本校为其他机构
院系归属:
医药化工学院
摘要:
Alzheimer's disease (AD) has become one of the most serious societal problems globally, with no effective treatments. Parenchymal accumulation of amyloid beta (Abeta) plaques and the formation of neurofibrillary tangles are the hallmarks of AD. Their possible interactions and synergistic effects in AD have been gradually elucidated. The failure of many clinical trials suggests that it is difficult to treat AD with a focus on a single target. Instead, multiple targets may be an important direction for AD drug research. In this study, we used protoporphyrin IX (PX)-modified oxidized mesoporous carbon nanospheres (OMCN) (PX@OMCN@PEG(OP)@RVGs) as a novel AD multifunctional nanodrug having multiple targets. The nanodrug efficiently inhibits tau phosphorylation. In addition, the use of PX with focused ultrasound triggered the production of reactive oxygen species that significantly inhibited Abeta aggregation. Both approaches notably increased the cognitive level of APP/PS1 transgenic (Tg) mice and ultimately achieved dual-target inhibition of AD. Furthermore, the safe and effective delivery of PX across the blood-brain barrier (BBB) due to modification of the RVG peptide was demonstrated in vivo and in vitro. The favorable photothermal effect of the nanoparticles improved the BBB permeability of PX@OP@RVGs under near-infrared irradiation. The results demonstrated that the novel PX@OP@RVG multifunctional nanomedicine has a dual-target treatment capability for AD and can traverse the BBB, indicating the potential for the effective treatment of AD.
参考文献:
Airan RD, 2017, NANO LETT, V17, P652, DOI 10.1021/acs.nanolett.6b03517
Ban DK, 2016, ACS APPL MATER INTER, V8, P31587, DOI 10.1021/acsami.6b11549
Bittar A, 2018, NPJ VACCINES, V3, DOI 10.1038/s41541-018-0046-8
Chaturvedi K, 2015, NANOMEDICINE-UK, V10, P1569, DOI [10.2217/NNM.15.36, 10.2217/nnm.15.36]
Chen JX, 2011, BIOMATERIALS, V32, P1678, DOI 10.1016/j.biomaterials.2010.10.047

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