Physics of Fluids - Publications

Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study

Open Access
Journal of Controlled Release 363, 747–755 (2023)

Authors

	Benjamin van Elburg
	Joke Deprez
	Martin van den Broek
	S.C. De Smedt
	Michel Versluis
	Guillaume Lajoinie
	Ine Lentacker
	Tim Segers

BibTeΧ

@article{VANELBURG2023747,
title = {Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study},
journal = {Journal of Controlled Release},
volume = {363},
pages = {747-755},
year = {2023},
issn = {0168-3659},
doi = {https://doi.org/10.1016/j.jconrel.2023.09.047},
url = {https://www.sciencedirect.com/science/article/pii/S0168365923006429},
author = {Benjamin {van Elburg} and Joke Deprez and Martin {van den Broek} and Stefaan C. {De Smedt} and Michel Versluis and Guillaume Lajoinie and Ine Lentacker and Tim Segers},
keywords = {Sonoporation, Monodisperse microbubbles, Therapy, Ultrasound, Ultrasound contrast agents},
abstract = {Sonoporation is the process where intracellular drug delivery is facilitated by ultrasound-driven microbubble oscillations. Several mechanisms have been proposed to relate microbubble dynamics to sonoporation including shear and normal stress. The present work aims to gain insight into the role of microbubble size on sonoporation and thereby into the relevant mechanism(s) of sonoporation. To this end, we measured the sonoporation efficiency while varying microbubble size using monodisperse microbubble suspensions. Sonoporation experiments were performed in vitro on cell monolayers using a single ultrasound pulse with a fixed frequency of 1¬†MHz while the acoustic pressure amplitude and pulse length were varied at 250, 500, and 750¬†kPa, and 10, 100, and 1000¬†cycles, respectively. Sonoporation efficiency was quantified using flow cytometry by measuring the FITC-dextran (4¬†kDa and 2¬†MDa) fluorescence intensity in 10,000 cells per experiment to average out inherent variations in the bioresponse. Using ultra-high-speed imaging at 10 million frames per second, we demonstrate that the bubble oscillation amplitude is nearly independent of the equilibrium bubble radius at acoustic pressure amplitudes that induce sonoporation (‚â• 500¬†kPa). However, we show that sonoporation efficiency is strongly dependent on the equilibrium bubble size and that under all explored driving conditions most efficiently induced by bubbles with a radius of 4.7 Œºm. Polydisperse microbubbles with a typical ultrasound contrast agent size distribution perform almost an order of magnitude lower in terms of sonoporation efficiency than the 4.7-Œºm bubbles. We elucidate that for our system shear stress is highly unlikely the mechanism of action. By contrast, we show that sonoporation efficiency correlates well with an estimate of the bubble-induced normal stress.}
}