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通过表面钝化减轻碳纳米管神经传感器对小鼠小胶质细胞转录组和形态学的影响

Mitigation of Carbon Nanotube Neurosensor Induced Transcriptomic and Morphological Changes in Mouse Microglia with Surface Passivation.

作者信息

Yang Darwin, Yang Sarah J, Del Bonis-O'Donnell Jackson Travis, Pinals Rebecca L, Landry Markita P

机构信息

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, United States.

Innovative Genomics Institute (IGI), Berkeley, California 94720, United States.

出版信息

ACS Nano. 2020 Oct 27;14(10):13794-13805. doi: 10.1021/acsnano.0c06154. Epub 2020 Sep 25.

Abstract

Single-walled carbon nanotubes (SWCNT) are used in neuroscience for deep-brain imaging, neuron activity recording, measuring brain morphology, and imaging neuromodulation. However, the extent to which SWCNT-based probes impact brain tissue is not well understood. Here, we study the impact of (GT)-SWCNT dopamine nanosensors on SIM-A9 mouse microglial cells and show SWCNT-induced morphological and transcriptomic changes in these brain immune cells. Next, we introduce a strategy to passivate (GT)-SWCNT nanosensors with PEGylated phospholipids to improve both biocompatibility and dopamine imaging quality. We apply these passivated dopamine nanosensors to image electrically stimulated striatal dopamine release in acute mouse brain slices, and show that slices labeled with passivated nanosensors exhibit higher fluorescence response to dopamine and measure more putative dopamine release sites. Hence, this facile modification to SWCNT-based dopamine probes provides immediate improvements to both biocompatibility and dopamine imaging functionality with an approach that is readily translatable to other SWCNT-based neurotechnologies.

摘要

单壁碳纳米管(SWCNT)在神经科学中用于深部脑成像、神经元活动记录、测量脑形态以及神经调节成像。然而,基于SWCNT的探针对脑组织的影响程度尚未得到充分了解。在此,我们研究了(GT)-SWCNT多巴胺纳米传感器对SIM-A9小鼠小胶质细胞的影响,并展示了SWCNT在这些脑免疫细胞中诱导的形态和转录组变化。接下来,我们引入了一种用聚乙二醇化磷脂钝化(GT)-SWCNT纳米传感器的策略,以提高生物相容性和多巴胺成像质量。我们将这些钝化的多巴胺纳米传感器应用于急性小鼠脑切片中电刺激纹状体多巴胺释放的成像,并表明用钝化纳米传感器标记的切片对多巴胺表现出更高的荧光响应,且能检测到更多假定的多巴胺释放位点。因此,这种对基于SWCNT的多巴胺探针的简便修饰,通过一种易于转化为其他基于SWCNT的神经技术的方法,立即改善了生物相容性和多巴胺成像功能。

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