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Cited by 607Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryBarrier Structure and Function Studies

Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

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Yuan, Dongfen, Zhao, Yuling, Banks, William A., Bullock, Kristin M., Haney, Matthew, Batrakova, Elena, Kabanov, Alexander V.·2017·Biomaterials
DOI 10.1016/j.biomaterials.2017.07.011PMC PMC5603188
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Abstract

Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB. Notably, upregulation of ICAM-1, a common process in inflammation, promotes Mϕ exosomes uptake in the BBB cells. We further demonstrate in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the BBB and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain. This delivery is enhanced in the presence of brain inflammation, a condition often present in CNS diseases. Taken together, the findings are of interest to basic science and possible use of Mϕ-derived exosomes as nanocarriers for brain delivery of therapeutic proteins to treat CNS diseases.

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  • The engineered exosomes could cross the multiple layers of the blood-brain-barrier and target cancer cells within the brain tissue.

    “Importantly, the engineered exosomes could cross the multiple layers of the blood-brain-barrier (BBB) and target cancer cells within the brain tissue (40, 65–68).”

    From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [68]

    The Conclusion and Future Directions section says macrophage exosomes can cross the BBB and carry cargo into brain tissue, particularly under inflammation. It does not show that they target cancer cells, and it expressly limits its barrier conclusion to the vascular barrier rather than multiple barriers. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Yuan, D., Zhao, Y., Banks, W. A., Bullock, K. M., Haney, M., Batrakova, E., & Kabanov, A. V.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of Washington (US)
  • VA Puget Sound Health Care System (US)
Corresponding author
Kabanov, Alexander V.
ORCID
Venue
Biomaterials
Publisher
Elsevier BV
Published
2017-10
Volume
142
Pages
1-12
ISSN
0142-9612 (ISSN-L)
DOI
10.1016/j.biomaterials.2017.07.011
PMC
PMC5603188
OpenAlex
W2736233594
Cited by
607
References
5
Citations by year
2026: 33 · 2025: 77 · 2024: 103 · 2023: 81 · 2022: 79 · 2021: 95 · 2020: 66 · 2019: 44 · 2018: 24 · 2017: 5
FWCI
15.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (1R21 NS088152, RO1 NS36229)
  • Rettsyndrome.org HeART (3112)
  • UNC Eshelman School of Pharmacy
  • University Cancer Research Fund
  • Cancer Center Core (P30 CA016086)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
blood-brain barrier penetration, neuroinflammation, ICAM-1, LFA-1, C-type lectin receptors, brain microvascular endothelial cells, brain drug delivery, intravenous administration
MeSH terms
RAW 264.7 Cells, Animals, Brain, Drug Carriers, Humans, Inflammation, Macrophages, Tissue Distribution, Lymphocyte Function-Associated Antigen-1, Drug Delivery Systems, Intercellular Adhesion Molecule-1, Brain-Derived Neurotrophic Factor, Lectins, C-Type, Endothelial Cells, Mice, Nanoparticles, Exosomes, Microvessels

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