title: 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.affiliation: Inserm, U1032, LabTAU, Lyon, France; Inserm, U1033, Lyon, France; University of Lyon, Lyon, France; LabEx DEVweCAN, Lyon, France. Electronic address: sophie.tardoski@inserm.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tardoski
authors.affiliation: Inserm, U1033, Lyon, France; University of Lyon, Lyon, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gineyts
authors.affiliation: Inserm, U1032, LabTAU, Lyon, France; University of Lyon, Lyon, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ngo
authors.affiliation: Inserm, U1032, LabTAU, Lyon, France; University of Lyon, Lyon, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kocot
authors.affiliation: University of Lyon, Lyon, France; LabEx DEVweCAN, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Clézardin
authors.affiliation: University of Lyon, Lyon, France; LabEx DEVweCAN, Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Melodelima
mesh_terms: D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002966:Clathrin / Q000378:metabolism*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004357:Drug Synergism; D053672:Electrochemotherapy / Q000379:methods*; D004705:Endocytosis / Q000528:radiation effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061986:MCF-7 Cells; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D002966:Clathrin; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonate; Bone metastasis; Breast cancer; Drug delivery; Ultrasound; Zoledronic acid