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 language | English |
|---|---|
| Article number | 119250 |
| Journal | Biomaterials |
| Volume | 217 |
| Early online date | 27 Jun 2019 |
| DOIs | |
| Publication status | Published - 1 Oct 2019 |
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Keywords
- Drug delivery
- Loaded microbubbles
- Mechanisms
- Microbubbles
- Radiation forces
- Ultrasound
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}
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 journal › Article › Academic › peer-review
TY - JOUR
T1 - Sonoprinting of nanoparticle-loaded microbubbles
T2 - Unraveling the multi-timescale mechanism
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
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Loaded microbubbles
KW - Mechanisms
KW - Microbubbles
KW - Radiation forces
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85068446766&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2019.119250
DO - 10.1016/j.biomaterials.2019.119250
M3 - Article
VL - 217
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
M1 - 119250
ER -