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Adv Mater. 2019 Feb 25:e1807557. doi: 10.1002/adma.201807557. [Epub ahead of print]

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

Author information

1
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, USA.
2
College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
3
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
4
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, 650118, China.
5
Department of Neurosurgery, University of California, Los Angeles, CA, 90095, USA.
6
Department of Orthopedic Surgery, University of California, San Diego, San Diego, CA, 92093, USA.
7
Tianjin Neurological Institute, MOE Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, The General Hospital of Tianjin Medical University, Tianjin, 300052, China.
8
UCLA AIDS Institute, Los Angeles, CA, 90095, USA.
9
Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
10
Beijing Institute of Biotechnology, Beijing, 100071, China.

Abstract

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.

KEYWORDS:

blood-brain barrier penetration; central nervous system delivery; nanocapsules; nanomedicine

PMID:
30803073
DOI:
10.1002/adma.201807557

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