Physics of Fluids - Publications

Sonoprinting of nanoparticle-loaded microbubbles: Unraveling the multi-timescale mechanism

Biomaterials 217, 119250 (2019)

Authors

	S. Roovers
	Guillaume Lajoinie
	Ine De Cock
	Toon Brans
	Heleen Dewitte
	K. Braeckmans
	Michel Versluis
	S.C. De Smedt
	Ine Lentacker

BibTeΧ

@article{ROOVERS2019119250,
title = "Sonoprinting of nanoparticle-loaded microbubbles: Unraveling the multi-timescale mechanism",
journal = "Biomaterials",
volume = "217",
pages = "119250",
year = "2019",
issn = "0142-9612",
doi = "https://doi.org/10.1016/j.biomaterials.2019.119250",
url = "http://www.sciencedirect.com/science/article/pii/S0142961219303497",
author = "Silke Roovers and Guillaume Lajoinie and Ine De Cock and Toon Brans and Heleen Dewitte and Kevin Braeckmans and Michel Versuis and Stefaan C. De Smedt and Ine Lentacker",
keywords = "Ultrasound, Microbubbles, Drug delivery, Loaded microbubbles, Mechanisms, Radiation forces",
abstract = "Ultrasound-triggered microbubble-assisted drug delivery is a promising tool for localized therapy. Several studies have shown the potential of nanoparticle-loaded microbubbles to effectively enhance the delivery of therapeutic agents to target tissue. We recently discovered that nanoparticle-carrying microbubbles can deposit the nanoparticles in patches onto cell membranes, a process which we termed ‘sonoprinting’. However, the biophysical mechanisms behind sonoprinting are not entirely clear. In addition, the question remains how the ultrasound parameters, such as acoustic pressure and pulse duration, influence sonoprinting. Aiming for a better understanding of sonoprinting, this report investigates the behavior of nanoparticle-loaded microbubbles under ultrasound exposure, making use of three advanced optical imaging techniques with frame rates ranging from 5 frames per second to 10 million frames per second, to capture the biophysical cell-bubble interactions that occur on a multitude of timescales. We observed that non-spherically oscillating microbubbles release their nanoparticle payload in the first few cycles of ultrasound insonation. At low acoustic pressures, the released nanoparticles are transported away from the cells by microstreaming, which does not favor uptake of the nanoparticles by the cells. However, higher acoustic pressures (>300 kPa) and longer ultrasound pulses (>100 cycles) lead to rapid translation of the microbubbles, due to acoustic radiation forces. As a result, the released nanoparticles are transported along in the wake of the microbubbles, which eventually leads to the deposition of nanoparticles in elongated patches on the cell membrane, i.e. sonoprinting. We conclude that a sufficiently high acoustic pressure and long pulses are needed for sonoprinting of nanoparticles on cells."
}