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Open AccessArticle

Potential Use of Extracellular Vesicles Generated by Microbubble-Assisted Ultrasound as Drug Nanocarriers for Cancer Treatment

1
Imaging Division, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
2
Department of Biomedical Engineering, TU Eindhoven, 5600 MB Eindhoven, The Netherlands
3
Department of Pharmaceutical Sciences, University of Utrecht, 3584 CG Utrecht, The Netherlands
4
Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 3024; https://doi.org/10.3390/ijms21083024
Received: 1 April 2020 / Revised: 17 April 2020 / Accepted: 22 April 2020 / Published: 24 April 2020
(This article belongs to the Special Issue Extracellular Vesicles: Biology and Potentials in Cancer Therapeutics)
Extracellular vesicles (EVs)-carrying biomolecules derived from parental cells have achieved substantial scientific interest for their potential use as drug nanocarriers. Ultrasound (US) in combination with microbubbles (MB) have been shown to trigger the release of EVs from cancer cells. In the current study, the use of microbubbles-assisted ultrasound (USMB) to generate EVs containing drug cargo was investigated. The model drug, CellTracker™ green fluorescent dye (CTG) or bovine serum albumin conjugated with fluorescein isothiocyanate (BSA FITC) was loaded into primary human endothelial cells in vitro using USMB. We found that USMB loaded CTG and BSA FITC into human endothelial cells (HUVECs) and triggered the release of EVs containing these compounds in the cell supernatant within 2 h after treatment. The amount of EV released seemed to be correlated with the increase of US acoustic pressure. Co-culturing these EVs resulted in uptake by the recipient tumour cells within 4 h. In conclusion, USMB was able to load the model drugs into endothelial cells and simultaneously trigger the release of EVs-carrying model drugs, highlighting the potential of EVs as drug nanocarriers for future drug delivery in cancer. View Full-Text
Keywords: drug delivery; extracellular vesicles; lysosome; nanocarriers; ultrasound drug delivery; extracellular vesicles; lysosome; nanocarriers; ultrasound
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MDPI and ACS Style

Yuana, Y.; Balachandran, B.; van der Wurff-Jacobs, K.M.G.; Schiffelers, R.M.; Moonen, C.T. Potential Use of Extracellular Vesicles Generated by Microbubble-Assisted Ultrasound as Drug Nanocarriers for Cancer Treatment. Int. J. Mol. Sci. 2020, 21, 3024.

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