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  • Mechanisms of the ultrasound-mediated intracellular delivery of liposomes and dextrans.

Mechanisms of the ultrasound-mediated intracellular delivery of liposomes and dextrans.

IEEE transactions on ultrasonics, ferroelectrics, and frequency control (2013-01-05)
Mercy Afadzi, Sabina P Strand, Esben A Nilssen, Svein-Erik Måsøy, Tonni F Johansen, Rune Hansen, Bjørn A Angelsen, Catharina de L Davies
摘要

The mechanism involved in the ultrasoundenhanced intracellular delivery of fluorescein-isothiocyanate (FITC)-dextran (molecular weight 4 to 2000 kDa) and liposomes containing doxorubicin (Dox) was studied using HeLa cells and an ultrasound transducer at 300 kHz, varying the acoustic power. The cellular uptake and cell viability were measured using flow cytometry and confocal microscopy. The role of endocytosis was investigated by inhibiting clathrin- and caveolae-mediated endocytosis, as well as macropinocytosis. Microbubbles were found to be required during ultrasound treatment to obtain enhanced cellular uptake. The percentage of cells internalizing Dox and dextran increased with increasing mechanical index. Confocal images and flow cytometric analysis indicated that the liposomes were disrupted extracellularly and that released Dox was taken up by the cells. The percentage of cells internalizing dextran was independent of the molecular weight of dextrans, but the amount of the small 4-kDa dextran molecules internalized per cell was higher than for the other dextrans. The inhibition of endocytosis during ultrasound exposure resulted in a significant decrease in cellular uptake of dextrans. Therefore, the improved uptake of Dox and dextrans may be a result of both sonoporation and endocytosis.

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Sigma-Aldrich
异硫氰酸荧光素-葡聚糖, average mol wt 2,000,000
Sigma-Aldrich
异硫氰酸荧光素-葡聚糖, average mol wt 2,000,000