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

ABSTRACT: 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.

SUBMITTER: Yuana Y

PROVIDER: S-EPMC7216118 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Yuana Yuana Y Balachandran Banuja B van der Wurff-Jacobs Kim M G KMG Schiffelers Raymond M RM Moonen Chrit T CT

International journal of molecular sciences 20200424 8

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 ...[more]

PMID: 32344752

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Project description:Microbubble (MB)-assisted ultrasound (US) is a promising physical method to increase non-invasively, transiently, and precisely the permeability of the blood-brain barrier (BBB) to therapeutic molecules. Previous preclinical studies established the innocuity of this procedure using complementary analytical strategies including transcriptomics, histology, brain imaging, and behavioral tests. This cross-sectional study using rats aimed to investigate the metabolic processes following acoustically-mediated BBB opening in vivo using multimodal and multimatrices metabolomics approaches. After intravenous injection of MBs, the right striata were exposed to 1-MHz sinusoidal US waves at 0.6 MPa peak negative pressure with a burst length of 10 ms, for 30 s. Then, the striata, cerebrospinal fluid (CSF), blood serum, and urine were collected during sacrifice in three experimental groups at 3 h, 2 days, and 1 week after BBB opening (BBBO) and were compared to a control group where no US was applied. A well-established analytical workflow using nuclear magnetic resonance spectrometry and non-targeted and targeted high-performance liquid chromatography coupled to mass spectrometry were performed on biological tissues and fluids. In our experimental conditions, a reversible BBBO was observed in the striatum without physical damage or a change in rodent weight and behavior. Cerebral, peri-cerebral, and peripheral metabolomes displayed specific and sequential metabolic kinetics. The blood serum metabolome was more impacted in terms of the number of perturbated metabolisms than in the CSF, the striatum, and the urine. In addition, perturbations of arginine and arginine-related metabolisms were detected in all matrices after BBBO, suggesting activation of vasomotor processes and bioenergetic supply. The exploration of the tryptophan metabolism revealed a transient vascular inflammation and a perturbation of serotoninergic neurotransmission in the striatum. For the first time, we characterized the metabolic signature following the acoustically-mediated BBBO within the striatum and its surrounding biological compartments.

Dataset Information

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

Publications

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

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