title: Over-pressure suppresses ultrasonic-induced drug uptake.
abstract: Ultrasound (US) is used to enhance and target delivery of drugs and genes to cancer tissues. The present study further examines the role of acoustic cavitation in US-induced permeabilization of cell membranes and subsequent drug or gene uptake by the cell. Rat colon cancer cells were exposed to ultrasound at various static pressures to examine the hypothesis that oscillating bubbles, also known as cavitating bubbles, permeabilize cells. Increasing pressure suppresses bubble cavitation activity; thus, if applied pressure were to reduce drug uptake, cell permeabilization would be strongly linked to bubble cavitation activity. Cells were exposed to 476 kHz pulsed ultrasound at average intensities of 2.75 W/cm(2) and 5.5 W/cm(2) at various pressures and times in an isothermal chamber. Cell fractions with reversible membrane damage (calcein uptake) and irreversible damage (propidium iodide uptake) were analyzed by flow cytometry. Pressurization to 3 atm nearly eliminated the biological effect of US in promoting calcein uptake. Data also showed a linear increase in membrane permeability with respect to insonation time and intensity. This research shows that US-mediated cell membrane permeability is likely linked to cavitation bubble activity.
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: S Briant
authors.initials: SB
authors.lastname: Stringham
authors.forename: Maria A
authors.initials: MA
authors.lastname: Viskovska
authors.forename: Eric S
authors.initials: ES
authors.lastname: Richardson
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Ghaleb A
authors.initials: GA
authors.lastname: Husseini
authors.forename: Byron K
authors.initials: BK
authors.lastname: Murray
authors.forename: William G
authors.initials: WG
authors.lastname: Pitt
mesh_terms: D000818:Animals; D016923:Cell Death; D002463:Cell Membrane Permeability; D003110:Colonic Neoplasms / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry / Q000379:methods; D005452:Fluoresceins / Q000493:pharmacokinetics; D006874:Hydrostatic Pressure; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D045423:Microbubbles; D011312:Pressure; D051381:Rats; D013010:Sonication / Q000295:instrumentation / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D005452:Fluoresceins; D007202:Indicators and Reagents; C007740:fluorexon