Low-Intensity Ultrasound Promotes Clathrin-Dependent Endocytosis for Drug Penetration into Tumor Cells.

Abstract

Ultrasound-mediated drug delivery is a field of research with promising results, although the exact mechanisms underlying intracellular delivery of therapeutic compounds remain to be elucidated. Many studies use drug carriers and cavitation to enhance drug uptake into tumor cells. However, cavitation could induce cell lysis and remain difficult to control and predict in vivo. In this study, low-intensity ultrasound was delivered using two transducers working at 2.9 and 1.3 MHz. The maximal peak negative pressure was 0.29 MPa to avoid cavitation. Low-intensity ultrasound induced clathrin-mediated endocytosis and forced the penetration of a bisphosphonate (zoledronic acid) into MCF-7 human breast cancer cells potentially as a result of mechanical stresses. When sonication parameters were adjusted to create mild hyperthermia in addition to the mechanical stress, further significant accumulation of ZOL was observed. These results provide better insight into the role of acoustic parameters in drug uptake.

• Authors: Sophie Tardoski, Evelyne Gineyts, Jacqueline Ngo, Anthony Kocot, Philippe Clézardin, David Melodelima
• Journal: Ultrasound in medicine & biology (Ultrasound Med Biol) Vol. 41 Issue 10 Pg. 2740-54 (Oct 2015) ISSN: 1879-291X [Electronic] England
• PMID: 26213291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bone Density Conservation Agents
• Clathrin
• Diphosphonates
• Imidazoles
• Zoledronic Acid

Topics

• Bone Density Conservation Agents (administration & dosage, pharmacokinetics)
• Clathrin (metabolism)
• Diphosphonates (administration & dosage, pharmacokinetics)
• Drug Synergism
• Electrochemotherapy (methods)
• Endocytosis (radiation effects)
• Humans
• Imidazoles (administration & dosage, pharmacokinetics)
• MCF-7 Cells
• Radiation Dosage
• Sonication (methods)
• Zoledronic Acid