Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source
Extracellular vesicles (EVs) represent a next generation drug delivery system that combines nanoparticle size with extraordinary ability to cross biological barriers, reduced immunogenicity, and low offsite toxicity profiles. A successful application of this natural way of delivering biological comp...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2021-12-01
|
| Series: | Advanced NanoBiomed Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/anbr.202100064 |
| _version_ | 1797823804364292096 |
|---|---|
| author | Matthew J. Haney Yuling Zhao John K. Fallon Yue Wang Samuel M. Li Emily E. Lentz Dorothy Erie Philip C. Smith Elena V. Batrakova |
| author_facet | Matthew J. Haney Yuling Zhao John K. Fallon Yue Wang Samuel M. Li Emily E. Lentz Dorothy Erie Philip C. Smith Elena V. Batrakova |
| author_sort | Matthew J. Haney |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) represent a next generation drug delivery system that combines nanoparticle size with extraordinary ability to cross biological barriers, reduced immunogenicity, and low offsite toxicity profiles. A successful application of this natural way of delivering biological compounds requires deep understanding EVs intrinsic properties inherited from their parent cells. Herein, EVs released by cells of different origin, with respect to drug delivery to the brain for treatment of neurodegenerative disorders, are evaluated. The morphology, size, and zeta potential of EVs secreted by primary macrophages (mEVs), neurons (nEVs), and astrocytes (aEVs) are examined by nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and atomic force microscopy (AFM). Spherical nanoparticles with average size 110–130 nm and zeta potential around −20 mV are identified for all EVs types. mEVs show the highest levels of tetraspanins and integrins compared with nEVs and aEVs, suggesting superior adhesion and targeting to the inflamed tissues by mEVs. Strikingly, aEVs are preferentially taken up by neuronal cells in vitro, followed by mEVs and nEVs. Nevertheless, the brain accumulation levels of mEVs in a transgenic mouse model of Parkinson's disease are significantly higher than those of nEVs or aEVs. Therefore, mEVs are suggested as the most promising nanocarrier system for drug delivery to the brain. |
| first_indexed | 2024-03-13T10:29:28Z |
| format | Article |
| id | doaj.art-ee15ab4b4ebf4cac89bb0ef3ebb803ec |
| institution | Directory Open Access Journal |
| issn | 2699-9307 |
| language | English |
| last_indexed | 2024-03-13T10:29:28Z |
| publishDate | 2021-12-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj.art-ee15ab4b4ebf4cac89bb0ef3ebb803ec2023-05-19T03:06:29ZengWiley-VCHAdvanced NanoBiomed Research2699-93072021-12-01112n/an/a10.1002/anbr.202100064Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell SourceMatthew J. Haney0Yuling Zhao1John K. Fallon2Yue Wang3Samuel M. Li4Emily E. Lentz5Dorothy Erie6Philip C. Smith7Elena V. Batrakova8Center for Nanotechnology in Drug Delivery University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAEshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAEshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAEshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACollege of Arts and Sciences University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACollege of Arts and Sciences University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAEshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAExtracellular vesicles (EVs) represent a next generation drug delivery system that combines nanoparticle size with extraordinary ability to cross biological barriers, reduced immunogenicity, and low offsite toxicity profiles. A successful application of this natural way of delivering biological compounds requires deep understanding EVs intrinsic properties inherited from their parent cells. Herein, EVs released by cells of different origin, with respect to drug delivery to the brain for treatment of neurodegenerative disorders, are evaluated. The morphology, size, and zeta potential of EVs secreted by primary macrophages (mEVs), neurons (nEVs), and astrocytes (aEVs) are examined by nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and atomic force microscopy (AFM). Spherical nanoparticles with average size 110–130 nm and zeta potential around −20 mV are identified for all EVs types. mEVs show the highest levels of tetraspanins and integrins compared with nEVs and aEVs, suggesting superior adhesion and targeting to the inflamed tissues by mEVs. Strikingly, aEVs are preferentially taken up by neuronal cells in vitro, followed by mEVs and nEVs. Nevertheless, the brain accumulation levels of mEVs in a transgenic mouse model of Parkinson's disease are significantly higher than those of nEVs or aEVs. Therefore, mEVs are suggested as the most promising nanocarrier system for drug delivery to the brain.https://doi.org/10.1002/anbr.202100064cell sourcedrug deliveryextracellular vesiclesneuroinflammationParkinson's diseasetargeted proteomics |
| spellingShingle | Matthew J. Haney Yuling Zhao John K. Fallon Yue Wang Samuel M. Li Emily E. Lentz Dorothy Erie Philip C. Smith Elena V. Batrakova Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source Advanced NanoBiomed Research cell source drug delivery extracellular vesicles neuroinflammation Parkinson's disease targeted proteomics |
| title | Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source |
| title_full | Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source |
| title_fullStr | Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source |
| title_full_unstemmed | Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source |
| title_short | Extracellular Vesicles as Drug Delivery System for the Treatment of Neurodegenerative Disorders: Optimization of the Cell Source |
| title_sort | extracellular vesicles as drug delivery system for the treatment of neurodegenerative disorders optimization of the cell source |
| topic | cell source drug delivery extracellular vesicles neuroinflammation Parkinson's disease targeted proteomics |
| url | https://doi.org/10.1002/anbr.202100064 |
| work_keys_str_mv | AT matthewjhaney extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT yulingzhao extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT johnkfallon extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT yuewang extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT samuelmli extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT emilyelentz extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT dorothyerie extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT philipcsmith extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource AT elenavbatrakova extracellularvesiclesasdrugdeliverysystemforthetreatmentofneurodegenerativedisordersoptimizationofthecellsource |