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

(2019) BIOMATERIALS. 217.
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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 nano particle payload in the first few cycles of ultrasound insonation. At low acoustic pressures, the released nano particles are transported away from the cells by microstreaming, which does not favor uptake of the nano particles 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.
Keywords
Ultrasound, Microbubbles, Drug delivery, Loaded microbubbles, Mechanisms, Radiation forces, ACOUSTIC RADIATION FORCE, CONTRAST AGENTS, DRUG-DELIVERY, ULTRASOUND EXPOSURE, ENDOTHELIAL-CELLS, GENE DELIVERY, WALL, SONOPORATION, OPTIMIZATION, BEHAVIOR

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Citation

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Chicago
Roovers, Silke, Guillaume Lajoinie, Ine De Cock, Toon Brans, Heleen Dewitte, Kevin Braeckmans, Michel Versuis, Stefaan De Smedt, and Ine Lentacker. 2019. “Sonoprinting of Nanoparticle-loaded Microbubbles : Unraveling the Multi-timescale Mechanism.” Biomaterials 217.
APA
Roovers, S., Lajoinie, G., De Cock, I., Brans, T., Dewitte, H., Braeckmans, K., Versuis, M., et al. (2019). Sonoprinting of nanoparticle-loaded microbubbles : unraveling the multi-timescale mechanism. BIOMATERIALS, 217.
Vancouver
1.
Roovers S, Lajoinie G, De Cock I, Brans T, Dewitte H, Braeckmans K, et al. Sonoprinting of nanoparticle-loaded microbubbles : unraveling the multi-timescale mechanism. BIOMATERIALS. 2019;217.
MLA
Roovers, Silke et al. “Sonoprinting of Nanoparticle-loaded Microbubbles : Unraveling the Multi-timescale Mechanism.” BIOMATERIALS 217 (2019): n. pag. Print.
@article{8627590,
  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 nano particle payload in the first few cycles of ultrasound insonation. At low acoustic pressures, the released nano particles are transported away from the cells by microstreaming, which does not favor uptake of the nano particles 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.},
  articleno    = {119250},
  author       = {Roovers, Silke and Lajoinie, Guillaume and De Cock, Ine and Brans, Toon and Dewitte, Heleen and Braeckmans, Kevin and Versuis, Michel and De Smedt, Stefaan and Lentacker, Ine},
  issn         = {0142-9612},
  journal      = {BIOMATERIALS},
  keywords     = {Ultrasound,Microbubbles,Drug delivery,Loaded microbubbles,Mechanisms,Radiation forces,ACOUSTIC RADIATION FORCE,CONTRAST AGENTS,DRUG-DELIVERY,ULTRASOUND EXPOSURE,ENDOTHELIAL-CELLS,GENE DELIVERY,WALL,SONOPORATION,OPTIMIZATION,BEHAVIOR},
  language     = {eng},
  pages        = {14},
  title        = {Sonoprinting of nanoparticle-loaded microbubbles : unraveling the multi-timescale mechanism},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2019.119250},
  volume       = {217},
  year         = {2019},
}

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