A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System

被引：100

作者：

Wu, Di ^{[1
]}

Qin, Meng ^{[2
]}

Xu, Duo ^{[1
]}

Wang, Lan ^{[3
,9
]}

Liu, Chaoyong ^{[2
]}

Ren, Jie ^{[1
]}

Zhou, George ^{[1
]}

Chen, Chen ^{[1
]}

Yang, Fengmei ^{[4
,5
]}

Li, Yanyan ^{[4
,5
]}

Zhao, Yuan ^{[4
,5
]}

Huang, Ruyi ^{[6
]}

Pourtaheri, Sina ^{[7
]}

Kang, Chunsheng ^{[8
]}

Kamata, Masakazu ^{[9
,10
]}

Chen, Irvin S. Y. ^{[3
,9
]}

He, Zhanlong ^{[4
,5
]}

Wen, Jing ^{[3
,9
]}

Chen, Wei ^{[11
]}

Lu, Yunfeng ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA

[2] Beijing Univ Chem Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Coll Life Sci & Technol, Beijing 100029, Peoples R China

[3] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[4] Chinese Acad Med Sci, Inst Med Biol, Kunming 650118, Yunnan, Peoples R China

[5] Peking Union Med Coll, Kunming 650118, Yunnan, Peoples R China

[6] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA

[7] Univ Calif San Diego, Dept Orthoped Surg, San Diego, CA 92093 USA

[8] Tianjin Med Univ, Gen Hosp, MOE Key Lab Postneuroinjury Neurorepair & Regener, Tianjin Neurol Inst, Tianjin 300052, Peoples R China

[9] UCLA, AIDS Inst, Los Angeles, CA 90095 USA

[10] UCLA, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA

[11] Beijing Inst Biotechnol, Beijing 100071, Peoples R China

来源：

ADVANCED MATERIALS | 2019年 / 31卷 / 18期

关键词：

blood-brain barrier penetration; central nervous system delivery; nanocapsules; nanomedicine; BLOOD-BRAIN-BARRIER; NICOTINIC ACETYLCHOLINE-RECEPTOR; HIGH-AFFINITY CHOLINE; FACTOR GENE-THERAPY; GROWTH-FACTOR; RAT-BRAIN; NANOPARTICLES; DRUG; TRANSPORTER; DISRUPTION;

D O I：

10.1002/adma.201807557

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Central nervous system (CNS) diseases are the leading cause of morbidity and mortality; their treatment, however, remains constrained by the blood-brain barrier (BBB) that impedes the access of most therapeutics to the brain. A CNS delivery platform for protein therapeutics, which is achieved by encapsulating the proteins within nanocapsules that contain choline and acetylcholine analogues, is reported herein. Mediated by nicotinic acetylcholine receptors and choline transporters, such nanocapsules can effectively penetrate the BBB and deliver the therapeutics to the CNS, as demonstrated in mice and non-human primates. This universal platform, in general, enables the delivery of any protein therapeutics of interest to the brain, opening a new avenue for the treatment of CNS diseases.

引用

页数：7

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