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细胞外囊泡介导的超小超顺磁性氧化铁纳米颗粒向小鼠脑内的递送

Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain.

作者信息

Kutchy Naseer A, Ma Rong, Liu Yutong, Buch Shilpa, Hu Guoku

机构信息

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States.

Department of Anatomy, Physiology, and Pharmacology, School of Veterinary Medicine, St. George's University, St. George's, Grenada.

出版信息

Front Pharmacol. 2022 Apr 7;13:819516. doi: 10.3389/fphar.2022.819516. eCollection 2022.

DOI:10.3389/fphar.2022.819516
PMID:35462907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9022024/
Abstract

Extracellular vesicles (EVs) are small lipid membrane-bound vesicles that can pass the blood-brain barrier. Therefore, EVs could be used for the delivery of therapeutics to the brain. Herein, we investigated the biodistribution of intranasal perfusion of ultrasmall superparamagnetic iron oxide (USPIO)-labeled astrocyte-derived EVs (ADEVs) in mice. We used Western blotting, transmission electron microscopy (TEM), and nanoparticle uptake assay to characterize ADEVs. In addition, intranasal perfusion coupled with magnetic resonance imaging (MRI) was employed to determine the distribution of USPIO-labeled ADEVs in mice. Our results showed the uptake of USPIO by mouse astrocytes and ADEVs. In addition, we confirmed the biodistribution of ADEVs in the brain and other internal organs, including the kidneys, liver, and spleen. Our results suggest that USPIO did not affect mouse astrocyte cell survivability and EV release. Therefore, intranasal delivery of therapeutic loaded EVs could be used for the treatment of various brain disorders.

摘要

细胞外囊泡（EVs）是一种小的脂质膜结合囊泡，能够穿过血脑屏障。因此，EVs可用于向大脑递送治疗药物。在此，我们研究了超小超顺磁性氧化铁（USPIO）标记的星形胶质细胞衍生的EVs（ADEVs）经鼻灌注在小鼠体内的生物分布。我们使用蛋白质免疫印迹法、透射电子显微镜（TEM）和纳米颗粒摄取试验来表征ADEVs。此外，采用经鼻灌注结合磁共振成像（MRI）来确定USPIO标记的ADEVs在小鼠体内的分布。我们的结果显示小鼠星形胶质细胞和ADEVs摄取了USPIO。此外，我们证实了ADEVs在大脑以及包括肾脏、肝脏和脾脏在内的其他内部器官中的生物分布。我们的结果表明，USPIO不影响小鼠星形胶质细胞的生存能力和EV释放。因此，经鼻递送负载治疗药物的EVs可用于治疗各种脑部疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/9022024/687f785904d6/fphar-13-819516-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/9022024/eb74d03a1abc/fphar-13-819516-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/9022024/687f785904d6/fphar-13-819516-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/9022024/eb74d03a1abc/fphar-13-819516-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/9022024/687f785904d6/fphar-13-819516-g002.jpg

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Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain.

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引用本文的文献

[1]
Advancements in extracellular vesicle therapy for neurodegenerative diseases.

Explor Neuroprotective Ther. 2025

[2]
Superparamagnetic Iron Oxide Nanoparticle-Labeled Extracellular Vesicles for Magnetic Resonance Imaging of Ischemic Stroke.

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[3]
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[4]
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[5]
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Transl Neurodegener. 2024-8-27

[6]
An Overview on the Physiopathology of the Blood-Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery.

Pharmaceutics. 2024-6-22

[7]
Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme.

Am J Cancer Res. 2024-2-15

[8]
Engineered extracellular vesicle-encapsulated CHIP as novel nanotherapeutics for treatment of renal fibrosis.

NPJ Regen Med. 2024-1-13

[9]
Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery.

Int J Mol Sci. 2023-12-29

[10]
Engineered Extracellular Vesicles: Emerging Therapeutic Strategies for Translational Applications.

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本文引用的文献

[1]
Astrocyte-Derived Extracellular Vesicle-Mediated Activation of Primary Ciliary Signaling Contributes to the Development of Morphine Tolerance.

Biol Psychiatry. 2021-10-15

[2]
Nanotechnologies for intranasal drug delivery: an update of literature.

Pharm Dev Technol. 2021-10

[3]
Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders.

Cell Mol Life Sci. 2021-6

[4]
Astrocyte-derived extracellular vesicles: A double-edged sword in central nervous system disorders.

Neurosci Biobehav Rev. 2021-6

[5]
IL-4/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

Proc Natl Acad Sci U S A. 2020-12-22

[6]
Engineered Extracellular Vesicles Loaded With miR-124 Attenuate Cocaine-Mediated Activation of Microglia.

Front Cell Dev Biol. 2020-7-30

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RNA delivery by extracellular vesicles in mammalian cells and its applications.

Nat Rev Mol Cell Biol. 2020-5-26

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Exosomes From Astrocyte Processes: Signaling to Neurons.

Front Pharmacol. 2019-12-2

[9]
Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics.

J Neuroimmune Pharmacol. 2020-9

[10]
Intranasal Delivery of lincRNA-Cox2 siRNA Loaded Extracellular Vesicles Decreases Lipopolysaccharide-Induced Microglial Proliferation in Mice.

J Neuroimmune Pharmacol. 2020-9

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