Mitochondria-targeted TPP-MoS2 with dual enzyme activity provides efficient neuroprotection through M1/M2 microglial polarization in an Alzheimer's disease model

被引：164

作者：

Ren, Chaoxiu ^{[1
]}

Li, Dandan ^{[1
]}

Zhou, Qixing ^{[1
]}

Hu, Xiangang ^{[1
]}

机构：

[1] Nankai Univ, Tianjin Key Lab Environm Remediat & Pollut Contro, Key Lab Pollut Proc & Environm Criteria, Minist Educ,Coll Environm Sci & Engn, Tianjin 300350, Peoples R China

来源：

BIOMATERIALS | 2020年 / 232卷

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; Targeting efficiency; Bifunctional nanozyme; Blood-brain barrier; Microglial polarization; OXIDATIVE STRESS; MOLYBDENUM-DISULFIDE; NANOPARTICLES; ANTIOXIDANTS; ACTIVATION; INHIBITION; DELIVERY; PROTEIN; CELLS; NEUROINFLAMMATION;

D O I：

10.1016/j.biomaterials.2019.119752

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Alzheimer's disease (AD) is one of the most common age-associated brain diseases and is induced by the accumulation of amyloid beta (A beta) and oxidative stress. Many studies have focused on eliminating A beta by nano particle affinity; however, nanoparticles are taken up mainly by microglia rather than neurons, leading poor control of AD. Herein, mitochondria-targeted nanozymes known as (3-carboxypropyl)triphenyl-phosphonium bromide-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]-functionalized molybdenum disulfide quantum dots (TPP-MoS2 QDs) were designed. TPP-MoS2 QDs mitigate A beta aggregate-mediated neurotoxicity and eliminate A beta aggregates in AD mice by switching microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. TPP-MoS2 QDs cross the blood-brain barrier, escape from lysosomes, target mitochondria and exhibit the comprehensive activity of a bifunctional nanozyme, thus preventing spontaneous neuroinflammation by regulating the proinflammatory substances interleuicin-1 beta, interleukin-6 and tumor necrosis factors as well as the anti-inflammatory substance transforming growth factor-beta. In contrast to the low efficacy of eliminating A beta by nanoparticle affinity, the present study provides a new pathway to mitigate AD pathology through mitochondria-targeted nanozymes and M1/M2 microglial polarization.

引用

页数：14