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Brain ischemia is the second leading cause of death and the third leading cause of disability in the world. Systemic delivery of microRNA, a class of molecules that regulate the expression of cellular proteins associated with angiogenesis, cell growth, proliferation and differentiation, holds great promise for the treatment of brain ischemia. However, their therapeutic efficacy has been hampered by poor delivery efficiency of microRNA. We report herein a platform technology based on microRNA nanocapsules, which enables their effective delivery to the disease sites in the brain. Exemplified by microRNA-21, intravenous injection of the nanocapsules into a rat model of cerebral ischemia could effectively ameliorate the infarct volume, neurological deficit and histopathological severity.


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Systemic delivery of microRNA for treatment of brain ischemia

Show Author's information Chaoyong Liu1,2,3,§Jing Wen7,§Dai Li1,2,§Hongzhao Qi6Lina Nih4Jialin Zhu1,2Duo Xu4Yu Ren8Shanshan Zhang6Donglin Han6Huanhuan Jia8Junhu Zhou1,2Meng Qin3Jialing Wu9Xubo Yuan6Ji Liu5( )Jin Zhao6( )Chunsheng Kang1,2 ( )Yunfeng Lu4( )
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
Key Laboratory of Post-Trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China
College of Life Science and Technology and Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Department of Medicine, Tianjin Huanhu Hospital, Tianjin 300350, China
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300350, China
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China
Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300350, China

§ Chaoyong Liu, Jing Wen, and Dai Li contributed equally to this work.

Abstract

Brain ischemia is the second leading cause of death and the third leading cause of disability in the world. Systemic delivery of microRNA, a class of molecules that regulate the expression of cellular proteins associated with angiogenesis, cell growth, proliferation and differentiation, holds great promise for the treatment of brain ischemia. However, their therapeutic efficacy has been hampered by poor delivery efficiency of microRNA. We report herein a platform technology based on microRNA nanocapsules, which enables their effective delivery to the disease sites in the brain. Exemplified by microRNA-21, intravenous injection of the nanocapsules into a rat model of cerebral ischemia could effectively ameliorate the infarct volume, neurological deficit and histopathological severity.

Keywords: polymer nanocapsules, small RNA delivery, microRNA-21, brain ischemia

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Publication history
Copyright
Acknowledgements

Publication history

Received: 14 November 2020
Revised: 10 February 2021
Accepted: 22 February 2021
Published: 26 April 2021
Issue date: September 2021

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2019YFA0903801), the National Natural Science Foundation of China (Nos. 52073015, 51773151, 52003021, and 81671169), Tianjin Municipal Health Bureau (No. 2010KY11), Postdoctoral Science Foundation of China (No. 2015M580212), and Fundamental Research Funds for the Central Universities (No. ZY2006).

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