Drug delivery strategies using drug-loaded extracellular vesicles generated by microbubble-assisted ultrasound

Project Name: Drug delivery strategies using drug-loaded extracellular vesicles generated by microbubble-assisted ultrasound
Status: Complete
Primary Site: Universitair Medisch Centrum Utrecht
Sponsor Organization: Focused Ultrasound Foundation
Funded Date: Dec 11, 2018
Funding Period: Dec 11, 2018 - Dec 10, 2019
Funding Program: Research Award
Category: MOA
Amount Awarded: $100,000.00

Abstract

Ultrasound (US) in combination with microbubbles (MB) represents an emerging approach for localized drug delivery. However, the micron size of MB implies that their effects are limited to the tumor vasculature and as a consequence the drug uptake by USMB application is limited to cells adjacent to vessels. Thus, some improvements in USMB-guided drug delivery are needed in order to also reach cells further distant from the vasculature. Our recent findings show that USMB triggers the release of cell-derived membrane- enclosed nanoparticles known as extracellular vesicles (EVs). Most of USMB-triggered EVs are much smaller (<200 nm) than MB, and thus may efficiently bypass the multiplicity of biological barriers (e.g. cell membrane, endothelial lining). Our research goal is to study whether the USMB-triggered EVs can be used as drug nanocarriers to increase the local drug concentration in tumors. We hypothesize that: (1) USMB can load the drug endogenously into EVs and (2) USMB-triggered EVs carrying drug are taken up by the recipient cells.

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