Targeted exosome coating gene-chem nanocomplex as "nanoscavenger" for clearing α-synuclein and immune activation of Parkinson's disease

被引：122

作者：

Liu, Linying ^{[1
,2
,3
]}

Li, Yan ^{[1
,2
]}

Peng, Huan ^{[1
,2
]}

Liu, Ruiyuan ^{[1
,2
]}

Ji, Weihong ^{[1
,2
]}

Shi, Zhuyan ^{[1
,2
]}

Shen, Jie ^{[1
,2
]}

Ma, Guanghui ^{[1
]}

Zhang, Xin ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Beijing Polytech, Coll Bioengn, Beijing 100176, Peoples R China

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 50期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

DENDRITIC CELLS; SIRNA DELIVERY; MOTOR DYSFUNCTION; CURCUMIN; BRAIN; AGGREGATION; INDUCTION; IL-10;

D O I：

10.1126/sciadv.aba3967

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The most critical problem in the treatment of neurodegenerative diseases is brain neuronal protection, which can be overcome by clearing pathological substances and regulating the immune environment. In the above treatment strategies, the traditional poor drug delivery problem is inevitable. Here, we show an engineering core-shell hybrid system named rabies virus glycoprotein (RVG) peptide-modified exosome (EXO) curcumin/phenylboronic acid-poly(2-(dimethylamino)ethyl acrylate) nanoparticle/small interfering RNA targeting SNCA (REXO-C/ANP/S). It is a nanoscavenger for clearing alpha-synuclein aggregates and reducing their cytotoxicity in Parkinson's disease neurons. The motor behavior of Parkinson's disease mice is substantially improved after REXO-C/ANP/S treatment. In particular, we demonstrate that REXO-C/ANP/S is also a nanoscavenger for clearing immune activation due to its natural immature dendritic cell EXO coating. Our findings show that REXO-C/ANP/S may serve as a platform for neurodegenerative diseases treatment.

引用

页数：11

共 39 条

[21] shRNA and siRNA delivery to the brain [J].

Pardridge, William M. .

ADVANCED DRUG DELIVERY REVIEWS, 2007, 59 (2-3) :141-152

[22] Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi-Based Immunochemotherapy of Intracranial Glioblastoma Treatment [J].

Qiao, Chenmeng ;

Yang, Jun ;

Shen, Qi ;

Liu, Ruiyuan ;

Li, Yanhui ;

Shi, Yuanjie ;

Chen, Jingli ;

Shen, Yanqin ;

Xiao, Zuobing ;

Weng, Jie ;

Zhang, Xin .

ADVANCED MATERIALS, 2018, 30 (18)

[23] Nitrated α-Synuclein-Induced Alterations in Microglial Immunity Are Regulated by CD4+ T Cell Subsets [J].

Reynolds, Ashley D. ;

Stone, David K. ;

Mosley, R. Lee ;

Gendelman, Howard E. .

JOURNAL OF IMMUNOLOGY, 2009, 182 (07) :4137-4149

[24] Engineering hybrid exosomes by membrane fusion with liposomes [J].

Sato, Yuko T. ;

Umezaki, Kaori ;

Sawada, Shinichi ;

Mukai, Sada-atsu ;

Sasaki, Yoshihiro ;

Harada, Naozumi ;

Shiku, Hiroshi ;

Akiyoshi, Kazunari .

SCIENTIFIC REPORTS, 2016, 6

[25] CD4+Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson's Disease [J].

Saunders, Jessica A. Hutter ;

Estes, Katherine A. ;

Kosloski, Lisa M. ;

Allen, Heather E. ;

Dempsey, Kathryn M. ;

Torres-Russotto, Diego R. ;

Meza, Jane L. ;

Santamaria, Pamela M. ;

Bertoni, John M. ;

Murman, Daniel L. ;

Ali, Hesham H. ;

Standaert, David G. ;

Mosley, R. Lee ;

Gendelman, Howard E. .

JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2012, 7 (04) :927-938

[26] Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection [J].

Sharma, Neha ;

Sharma, Sheetal ;

Nehru, Bimla .

INFLAMMOPHARMACOLOGY, 2017, 25 (03) :351-368

[27] Curcumin Modulates α-Synuclein Aggregation and Toxicity [J].

Singh, Pradeep K. ;

Kotia, Vasudha ;

Ghosh, Dhiman ;

Mohite, Ganesh M. ;

Kumar, Ashutosh ;

Maji, Samir K. .

ACS CHEMICAL NEUROSCIENCE, 2013, 4 (03) :393-407

[28] Surface Functionalization of Exosomes Using Click Chemistry [J].

Smyth, Tyson ;

Petrova, Krastina ;

Payton, Nicole M. ;

Persaud, Indushekhar ;

Redzic, Jasmina S. ;

Gruner, Michael W. ;

Smith-Jones, Peter ;

Anchordoquy, Thomas J. .

BIOCONJUGATE CHEMISTRY, 2014, 25 (10) :1777-1784

[29] Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease (vol 23, pg 123, 2018) [J].

Sommer, Annika ;

Marxreiter, Franz ;

Krach, Florian ;

Fadler, Tanja ;

Grosch, Janina ;

Maroni, Michele ;

Graef, Daniela ;

Eberhardt, Esther ;

Riemenschneider, Markus J. ;

Yeo, Gene W. ;

Kohl, Zacharias ;

Xiang, Wei ;

Gage, Fred H. ;

Winkler, Jurgen ;

Prots, Iryna ;

Winner, Beate .

CELL STEM CELL, 2019, 24 (06) :1006-1006

[30] A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells [J].

Son, YI ;

Egawa, SI ;

Tatsumi, T ;

Redlinger, RE ;

Kalinski, P ;

Kanto, T .

JOURNAL OF IMMUNOLOGICAL METHODS, 2002, 262 (1-2) :145-157

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