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Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant challenge. Nanoliposome-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution, delayed drug clearance, and restricted drug biodistribution for neural modulation. In this study, we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds (Nanolipo-Ru) to modulate neural activity and allow for real-time monitoring using the microelectrode arrays (MEAs). The Nanolipo-Ru nanoparticles had an average size of 134.10 ± 4.30 nm and exhibited excellent stability for seven weeks. For the in vivo experiment in the rat, release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4% and 81.6%, respectively. Simultaneously, the average power of local field potentials in the 0-15 Hz range degraded from 4.34 to 0.85 mW. In addition, the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the experiments. These results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal electrophysiology. Furthermore, nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.


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Nanoliposome-encapsulated caged-GABA for modulating neural electrophysiological activity with simultaneous detection by microelectrode arrays

Show Author's information Jingyu Xie1,2Yilin Song1,2Yuchuan Dai1,2Ziyue Li1,2Fei Gao1,2Xuanyu Li2,3Guihua Xiao1,2Yu Zhang1,2Hao Wang1,2Zeying Lu1,2Xingyu Jiang3,4Wenfu Zheng3Xinxia Cai1,2( )
State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China

Abstract

Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant challenge. Nanoliposome-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution, delayed drug clearance, and restricted drug biodistribution for neural modulation. In this study, we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds (Nanolipo-Ru) to modulate neural activity and allow for real-time monitoring using the microelectrode arrays (MEAs). The Nanolipo-Ru nanoparticles had an average size of 134.10 ± 4.30 nm and exhibited excellent stability for seven weeks. For the in vivo experiment in the rat, release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4% and 81.6%, respectively. Simultaneously, the average power of local field potentials in the 0-15 Hz range degraded from 4.34 to 0.85 mW. In addition, the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the experiments. These results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal electrophysiology. Furthermore, nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.

Keywords: microelectrode array, nanoliposome, neural modulation, light-sensitive drug

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Publication history
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Acknowledgements

Publication history

Received: 16 December 2019
Revised: 04 April 2020
Accepted: 17 April 2020
Published: 11 May 2020
Issue date: June 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was sponsored by the National Key Research and Development Program of nano science and technology of China (No. 2017YFA0205902), the National Natural Science Foundation of China (Nos. 61527815, 61960206012, 61975206, 61775216, 61971400, 61973292 and 61771452), and the Key Research Programs (Nos. QYZDJ-SSW-SYS015 and XDA16020902) of Frontier Sciences, CAS.

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