title: Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: implications for enhanced local drug delivery.
abstract: Liquid perfluorocarbon nanoparticles serve as sensitive and specific targeted contrast and drug delivery vehicles by binding to specific cell surface markers. We hypothesized that application of acoustic energy at diagnostic power levels could promote nanoparticle-associated drug delivery by stimulating increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane. Ultrasound (mechanical index = 1.9) applied with a conventional ultrasound imaging system to nanoparticles targeted to alpha(v)beta3-integrins on C32 melanoma cancer cells in vitro produced no untoward effects. Within 5 min, lipid delivery from nanoparticles into cell cytoplasm was dramatically augmented. We also demonstrate the operation of a potential physical mechanism for this effect, the acoustic radiation force on the nanoparticles, which may contribute to the enhanced lipid delivery. Accordingly, we propose that local delivery of lipophilic substances (e.g., drugs) from targeted nanoparticles directly into cell cytoplasm can be augmented rapidly and safely with conventional ultrasound imaging devices through nondestructive mechanisms.
authors.affiliation: Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Crowder
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Jon N
authors.initials: JN
authors.lastname: Marsh
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Barbieri
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Fuhrhop
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D049329:Nanostructures; D036103:Nanotechnology; D014465:Ultrasonics
chemical_list: D008055:Lipids