TY - JOUR
T1 - Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain
AU - Kutchy, Naseer A.
AU - Ma, Rong
AU - Liu, Yutong
AU - Buch, Shilpa
AU - Hu, Guoku
N1 - Funding Information:
We would like to thank the editor and reviewers for their constructive suggestions and critical comments on the manuscript. We are grateful to Yunlong Huang for his outstanding technical assistance and insightful discussions. We would like to thank Melissa Mellon and Lirong Xu from the Bioimaging Core (small animal MRI) for training Naseer with intranasal perfusion and MRI scanning. We would like to thank the Nebraska Center for Substance Abuse Research (NCSAR) for support. We would also like to thank Tom Bargar and Nicholas Conoan of the Electron Microscopy Core Facility (EMCF) at the University of Nebraska Medical Center for technical assistance. The EMCF is supported by state funds from the Nebraska Research Initiative (NRI) and the University of Nebraska Foundation and institutionally by the Office of the Vice-Chancellor for Research.
Funding Information:
This work was supported by startup funds from the University of Nebraska Medical Center and the National Institute of Health (NIH) (grants DA046831, DA042704, DA043138, and MH112848). This project was also supported by the NIH grant 2P30MH062261. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
Copyright © 2022 Kutchy, Ma, Liu, Buch and Hu.
PY - 2022/4/7
Y1 - 2022/4/7
N2 - 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.
AB - 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.
KW - brain drug delivery
KW - extracellular vesicles
KW - intranasal perfusion
KW - magnetic resonance imaging
KW - nanoparticles
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U2 - 10.3389/fphar.2022.819516
DO - 10.3389/fphar.2022.819516
M3 - Article
C2 - 35462907
AN - SCOPUS:85128714639
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 819516
ER -