Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration

Duo Xu; Di Wu; Meng Qin; Lina R Nih; Chaoyong Liu; Zheng Cao; Jie Ren; Xiangjun Chen; Zhanlong He; Wenhai Yu; Jiaoqiong Guan; Suqin Duan; Fang Liu; Xiangsheng Liu; Jesse Li; Dushawn Harley; Bin Xu; Lihua Hou; Irvin S Y Chen; Jing Wen; Wei Chen; Sina Pourtaheri; Yunfeng Lu

doi:10.1002/adma.201900727

Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration

Adv Mater. 2019 Aug;31(33):e1900727. doi: 10.1002/adma.201900727. Epub 2019 May 24.

Authors

Duo Xu¹, Di Wu¹, Meng Qin^{2

3}, Lina R Nih¹, Chaoyong Liu^{1

3}, Zheng Cao¹, Jie Ren¹, Xiangjun Chen⁴, Zhanlong He⁵, Wenhai Yu⁵, Jiaoqiong Guan⁵, Suqin Duan⁵, Fang Liu¹, Xiangsheng Liu⁶, Jesse Li⁷, Dushawn Harley⁷, Bin Xu^{1

8}, Lihua Hou⁹, Irvin S Y Chen², Jing Wen², Wei Chen⁹, Sina Pourtaheri⁷, Yunfeng Lu¹

Affiliations

¹ Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
² Department of Microbiology, Immunology, and Molecular Genetics, UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
³ College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Biotechnology, Beijing, 100029, China.
⁴ Department of Neurology, Huashan Hospital, Shanghai, 200040, China.
⁵ Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, 650118, China.
⁶ California NanoSystem Institute, Los Angeles, CA, 90095, USA.
⁷ Department of Orthopaedic Surgery, University of California, Los Angeles, CA, 90095, USA.
⁸ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, 130012, China.
⁹ Beijing Institute of Biotechnology, Beijing, 100029, China.

PMID: 31125138
DOI: 10.1002/adma.201900727

Abstract

The central nervous system (CNS) plays a central role in the control of sensory and motor functions, and the disruption of its barriers can result in severe and debilitating neurological disorders. Neurotrophins are promising therapeutic agents for neural regeneration in the damaged CNS. However, their penetration across the blood-brain barrier remains a formidable challenge, representing a bottleneck for brain and spinal cord therapy. Herein, a nanocapsule-based delivery system is reported that enables intravenously injected nerve growth factor (NGF) to enter the CNS in healthy mice and nonhuman primates. Under pathological conditions, the delivery of NGF enables neural regeneration, tissue remodeling, and functional recovery in mice with spinal cord injury. This technology can be utilized to deliver other neurotrophins and growth factors to the CNS, opening a new avenue for tissue engineering and the treatment of CNS disorders and neurodegenerative diseases.

Keywords: blood-brain barrier; central nervous system; nerve growth factors; neural regeneration; spinal cord injury.

MeSH terms

Acrylic Resins / chemistry
Animals
Biocompatible Materials / chemistry
Blood-Brain Barrier / metabolism*
Blood-Brain Barrier / ultrastructure
Cross-Linking Reagents / chemistry
Drug Liberation
Injections, Intravenous
Macaca mulatta
Methacrylates / chemistry
Mice, Inbred BALB C
Nanocapsules / chemistry*
Nerve Growth Factors / administration & dosage
Nerve Growth Factors / blood
Nerve Growth Factors / cerebrospinal fluid
Nerve Growth Factors / pharmacology*
Nerve Regeneration / drug effects*
PC12 Cells
Permeability
Phosphorylcholine / analogs & derivatives
Phosphorylcholine / chemistry
Polyesters / chemistry
Rats
Spinal Cord Injuries / drug therapy*
Spinal Cord Injuries / pathology
Spinal Cord Injuries / physiopathology

Substances

Acrylic Resins
Biocompatible Materials
Cross-Linking Reagents
Methacrylates
Nanocapsules
Nerve Growth Factors
Polyesters
Phosphorylcholine
poly(lactide)
carbopol 940
2-methacryloyloxyethyl phosphorylcholine