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

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number119250
JournalBiomaterials
Volume217
Early online date27 Jun 2019
DOIs
Publication statusPublished - 1 Oct 2019

Fingerprint

Microbubbles
Nanoparticles
Acoustics
Ultrasonics
Cell membranes
Cell Membrane
Blood Pressure
Pressure
Optical Imaging
Drug delivery
Cell Communication
Deposits
Radiation
Tissue
Imaging techniques

Keywords

  • Drug delivery
  • Loaded microbubbles
  • Mechanisms
  • Microbubbles
  • Radiation forces
  • Ultrasound

Cite this

Roovers, S., Lajoinie, G., De Cock, I., Brans, T., Dewitte, H., Braeckmans, K., ... Lentacker, I. (2019). Sonoprinting of nanoparticle-loaded microbubbles: Unraveling the multi-timescale mechanism. Biomaterials, 217, [119250]. https://doi.org/10.1016/j.biomaterials.2019.119250
Roovers, S. ; Lajoinie, Guillaume ; De Cock, Ine ; Brans, Toon ; Dewitte, Heleen ; Braeckmans, K. ; Versuis, Michel ; De Smedt, Stefaan C. ; Lentacker, Ine. / Sonoprinting of nanoparticle-loaded microbubbles : Unraveling the multi-timescale mechanism. In: Biomaterials. 2019 ; Vol. 217.
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Roovers, S, Lajoinie, G, De Cock, I, Brans, T, Dewitte, H, Braeckmans, K, Versuis, M, De Smedt, SC & Lentacker, I 2019, 'Sonoprinting of nanoparticle-loaded microbubbles: Unraveling the multi-timescale mechanism' Biomaterials, vol. 217, 119250. https://doi.org/10.1016/j.biomaterials.2019.119250

Sonoprinting of nanoparticle-loaded microbubbles : Unraveling the multi-timescale mechanism. / Roovers, S.; Lajoinie, Guillaume; De Cock, Ine; Brans, Toon; Dewitte, Heleen; Braeckmans, K.; Versuis, Michel; De Smedt, Stefaan C.; Lentacker, Ine.

In: Biomaterials, Vol. 217, 119250, 01.10.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Roovers, S.

AU - Lajoinie, Guillaume

AU - De Cock, Ine

AU - Brans, Toon

AU - Dewitte, Heleen

AU - Braeckmans, K.

AU - Versuis, Michel

AU - De Smedt, Stefaan C.

AU - Lentacker, Ine

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