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类淋巴系统及辅助途径促使纳米颗粒远离大脑。

Glymphatic System and Subsidiary Pathways Drive Nanoparticles Away from the Brain.

作者信息

Liu Rui, Jia Wenfeng, Wang Yushan, Hu Chuan, Yu Wenqi, Huang Yuan, Wang Ling, Gao Huile

机构信息

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

出版信息

Research (Wash D C). 2022 Mar 15;2022:9847612. doi: 10.34133/2022/9847612. eCollection 2022.

DOI:10.34133/2022/9847612
PMID:35360646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8943630/
Abstract

Although drug delivery systems (DDS) are efficient in brain delivery, they face failure in clinical settings due to their potential toxicity to the central nervous system. Little is known about where the DDS will go after brain delivery, and no specific elimination route that shares a passage with DDS has been verified. Hence, identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation. In this study, we investigated nonreactive gold nanoclusters, which can deliver into the brain, to determine the elimination route of DDS. Subsequently, nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations (77.8 ± 23.2% and 43.7 ± 23.4% contribution). Furthermore, the nanoclusters could be actively transported across the blood-brain barrier (BBB) by exosomes (30.5 ± 27.3% and 29.2 ± 7.1% contribution). In addition, microglia promoted glymphatic drainage and passage across the BBB. The simultaneous work of the glymphatic system, BBB, and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further brain-delivery DDS.

摘要

尽管药物递送系统（DDS）在脑部递送方面效率很高，但由于它们对中枢神经系统具有潜在毒性，在临床应用中面临失败。对于DDS在脑部递送后去向何处知之甚少，并且尚未证实有与DDS共享通道的特定消除途径。因此，确定用于脑部递送的无害DDS并确定它们在那里的命运将极大地促进其临床转化。在本研究中，我们研究了可递送至脑部的非反应性金纳米团簇，以确定DDS的消除途径。随后，对脑部的纳米团簇进行了系统追踪，发现它们主要通过类淋巴系统从血管基底膜引流到外周循环（贡献比例分别为77.8±23.2%和43.7±23.4%）。此外，纳米团簇可通过外泌体主动穿过血脑屏障（BBB）（贡献比例分别为30.5±27.3%和29.2±7.1%）。此外，小胶质细胞促进了类淋巴引流和穿过血脑屏障的过程。类淋巴系统、血脑屏障和小胶质细胞的协同作用揭示了用于脑部递送的金纳米团簇的命运，并为进一步的脑部递送DDS提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/49771ab0b701/RESEARCH2022-9847612.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/aa15211efa11/RESEARCH2022-9847612.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/513651bf7816/RESEARCH2022-9847612.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/4d595fa02375/RESEARCH2022-9847612.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/605e11f35c16/RESEARCH2022-9847612.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/2d03b8d426d5/RESEARCH2022-9847612.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/b8a3cd453c7f/RESEARCH2022-9847612.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/bab70e2ae84b/RESEARCH2022-9847612.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/48e4e3f436fb/RESEARCH2022-9847612.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/49771ab0b701/RESEARCH2022-9847612.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/aa15211efa11/RESEARCH2022-9847612.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/513651bf7816/RESEARCH2022-9847612.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/4d595fa02375/RESEARCH2022-9847612.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/605e11f35c16/RESEARCH2022-9847612.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/2d03b8d426d5/RESEARCH2022-9847612.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/b8a3cd453c7f/RESEARCH2022-9847612.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/bab70e2ae84b/RESEARCH2022-9847612.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/48e4e3f436fb/RESEARCH2022-9847612.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e36e/8943630/49771ab0b701/RESEARCH2022-9847612.009.jpg

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Acta Pharm Sin B. 2021 Dec;11(12):4032-4044. doi: 10.1016/j.apsb.2021.04.022. Epub 2021 May 7.
2
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Adv Sci (Weinh). 2021 Feb 24;8(9):2004025. doi: 10.1002/advs.202004025. eCollection 2021 May.
3
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4
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6
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5
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6
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7
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8
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9
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