title: RNA biomarker release with ultrasound and phase-change nanodroplets.
abstract: Microbubbles driven by ultrasound are capable of permeabilizing cell membranes and allowing biomarkers or therapeutics to exit from or enter cancer cells, respectively. Unfortunately, the relatively large size of microbubbles prevents extravasation. Lipid-based perfluorobutane microbubbles can be made seven-fold smaller by pressurization, creating 430-nm nanodroplets. The present study compares microbubbles and nanodroplets with respect to their ability to enhance miR-21 and mammaglobin mRNA release from cultured ZR-75-1 cells. Mammaglobin mRNA and miR-21 release increased with escalating concentrations of nanodroplets up to, respectively, 25- and 42-fold with 2% nanodroplets (v/v), compared with pre-ultrasound levels, whereas cell viability decreased to 62.4%. Sonication of ZR-75-1 cells incubated with microbubbles or nanodroplets caused relatively similar levels of cell death and miR-21 release, suggesting that nanodroplets are similar to microbubbles in enhancing cell permeability, but may be more advantageous because of their smaller size, which may allow extravasation through leaky tumor vasculature.
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Paproski
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Forbrich
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Hitt
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: rzemp@ualberta.ca.
authors.forename: Roger
authors.initials: R
authors.lastname: Zemp
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D001943:Breast Neoplasms; D016923:Cell Death; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D005466:Fluorocarbons; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C108042:perfluorobutane
keywords: Acoustic droplet vaporization; Mammaglobin; Nanodroplets; Perfluorobutane; Ultrasound; miR-21