title: Ultrasound-mediated intracellular drug delivery using microbubbles and temperature-sensitive liposomes.
abstract: A novel two-step protocol for intracellular drug delivery has been evaluated in vitro. As a first step TO-PRO-3 (a cell-impermeable dye that displays a strong fluorescence enhancement upon binding to nucleic acids) encapsulated in thermosensitive liposomes was released after heating to 42°C. A second step consisted of ultrasound-mediated local permeabilization of cell membrane allowing TO-PRO-3 internalization observable as nuclear staining. Only the combination of two consecutive steps - heating and sonication in the presence of SonoVue microbubbles led to the model drug TO-PRO-3 release from the thermosensitive liposomes and its intracellular uptake. This protocol is potentially beneficial for the intracellular delivery of cell impermeable drugs that suffer from rapid clearance and/or degradation in blood and are not intrinsically taken up by cells.
authors.affiliation: Laboratory IMF UMR 5231 CNRS/University Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Yudina
authors.forename: M
authors.initials: M
authors.lastname: de Smet
authors.forename: M
authors.initials: M
authors.lastname: Lepetit-Coiffé
authors.forename: S
authors.initials: S
authors.lastname: Langereis
authors.forename: L
authors.initials: L
authors.lastname: Van Ruijssevelt
authors.forename: P
authors.initials: P
authors.lastname: Smirnov
authors.forename: V
authors.initials: V
authors.lastname: Bouchaud
authors.forename: P
authors.initials: P
authors.lastname: Voisin
authors.forename: H
authors.initials: H
authors.lastname: Grüll
authors.forename: C T W
authors.initials: CT
authors.lastname: Moonen
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002232:Carbocyanines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004705:Endocytosis; D019220:High-Energy Shock Waves; D006358:Hot Temperature; D008027:Light; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D051381:Rats; D012542:Scattering, Radiation
chemical_list: D002232:Carbocyanines; D008055:Lipids; D008081:Liposomes; C098830:TO-PRO-3