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Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles

Microbubbles-assisted ultrasound (USMB) has shown promise in improving local drug delivery. The formation of transient membrane pores and endocytosis are reported to be enhanced by USMB, and they contribute to cellular drug uptake. Exocytosis also seems to be linked to endocytosis upon USMB treatmen...

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Autores principales: Yuana, Yuana, Jiang, Linglei, Lammertink, Bart H. A., Vader, Pieter, Deckers, Roel, Bos, Clemens, Schiffelers, Raymond M., Moonen, Chrit T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578002/
https://www.ncbi.nlm.nih.gov/pubmed/28757579
http://dx.doi.org/10.3390/ijms18081610
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author Yuana, Yuana
Jiang, Linglei
Lammertink, Bart H. A.
Vader, Pieter
Deckers, Roel
Bos, Clemens
Schiffelers, Raymond M.
Moonen, Chrit T.
author_facet Yuana, Yuana
Jiang, Linglei
Lammertink, Bart H. A.
Vader, Pieter
Deckers, Roel
Bos, Clemens
Schiffelers, Raymond M.
Moonen, Chrit T.
author_sort Yuana, Yuana
collection PubMed
description Microbubbles-assisted ultrasound (USMB) has shown promise in improving local drug delivery. The formation of transient membrane pores and endocytosis are reported to be enhanced by USMB, and they contribute to cellular drug uptake. Exocytosis also seems to be linked to endocytosis upon USMB treatment. Based on this rationale, we investigated whether USMB triggers exocytosis resulting in the release of extracellular vesicles (EVs). USMB was performed on a monolayer of head-and-neck cancer cells (FaDu) with clinically approved microbubbles and commonly used ultrasound parameters. At 2, 4, and 24 h, cells and EV-containing conditioned media from USMB and control conditions (untreated cells, cells treated with microbubbles and ultrasound only) were harvested. EVs were measured using flow cytometric immuno-magnetic bead capture assay, immunogold electron microscopy, and western blotting. After USMB, levels of CD9 exposing-EVs significantly increased at 2 and 4 h, whereas levels of CD63 exposing-EVs increased at 2 h. At 24 h, EV levels were comparable to control levels. EVs released after USMB displayed a heterogeneous size distribution profile (30–1200 nm). Typical EV markers CD9, CD63, and alix were enriched in EVs released from USMB-treated FaDu cells. In conclusion, USMB treatment triggers exocytosis leading to the release of EVs from FaDu cells.
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spelling pubmed-55780022017-09-05 Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles Yuana, Yuana Jiang, Linglei Lammertink, Bart H. A. Vader, Pieter Deckers, Roel Bos, Clemens Schiffelers, Raymond M. Moonen, Chrit T. Int J Mol Sci Communication Microbubbles-assisted ultrasound (USMB) has shown promise in improving local drug delivery. The formation of transient membrane pores and endocytosis are reported to be enhanced by USMB, and they contribute to cellular drug uptake. Exocytosis also seems to be linked to endocytosis upon USMB treatment. Based on this rationale, we investigated whether USMB triggers exocytosis resulting in the release of extracellular vesicles (EVs). USMB was performed on a monolayer of head-and-neck cancer cells (FaDu) with clinically approved microbubbles and commonly used ultrasound parameters. At 2, 4, and 24 h, cells and EV-containing conditioned media from USMB and control conditions (untreated cells, cells treated with microbubbles and ultrasound only) were harvested. EVs were measured using flow cytometric immuno-magnetic bead capture assay, immunogold electron microscopy, and western blotting. After USMB, levels of CD9 exposing-EVs significantly increased at 2 and 4 h, whereas levels of CD63 exposing-EVs increased at 2 h. At 24 h, EV levels were comparable to control levels. EVs released after USMB displayed a heterogeneous size distribution profile (30–1200 nm). Typical EV markers CD9, CD63, and alix were enriched in EVs released from USMB-treated FaDu cells. In conclusion, USMB treatment triggers exocytosis leading to the release of EVs from FaDu cells. MDPI 2017-07-25 /pmc/articles/PMC5578002/ /pubmed/28757579 http://dx.doi.org/10.3390/ijms18081610 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Yuana, Yuana
Jiang, Linglei
Lammertink, Bart H. A.
Vader, Pieter
Deckers, Roel
Bos, Clemens
Schiffelers, Raymond M.
Moonen, Chrit T.
Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title_full Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title_fullStr Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title_full_unstemmed Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title_short Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles
title_sort microbubbles-assisted ultrasound triggers the release of extracellular vesicles
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578002/
https://www.ncbi.nlm.nih.gov/pubmed/28757579
http://dx.doi.org/10.3390/ijms18081610
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