title: Observations on the viability of C6-glioma cells after sonoporation with low-intensity ultrasound and microbubbles.
abstract: Ultrasound (US) and microbubbles can be used to facilitate cellular uptake of drugs through a cavitationinduced enhancement of cell membrane permeability. The mechanism is, however, still incompletely understood. A direct contact between microbubbles and cell membrane is thought to be essential to create membrane perturbations lasting from seconds to minutes after US exposure of the cells. A recent study showed that the effect may even last up to 8 h after cavitation (with residual permeability up to 24 h after cavitation). In view of possible membrane damage, the purpose of this study was to further investigate the evolution of cell viability in the range of the 24-h temporal window. Furthermore, a description of the functional changes in tumor cells after US exposure was initiated to obtain a better understanding of the mechanism of membrane perturbation after sonication with microbubbles. Our results suggest that US does not reduce cell viability up to 24 h post-exposure. However, a perturbation of the entire cell population exposed to US was observed in terms of enzymatic activity and characteristics of the mitochondrial membrane. Furthermore, we demonstrated that US cavitation induces a transient loss of cell membrane asymmetry, resulting in phosphatidylserine exposure in the outer leaflet of the cell membrane.
authors.affiliation: Laboratory for Molecular and Functional Imaging: from Physiology to Therapy, FRE 3313 CNRS /Universite Bordeaux S egalen, Bordeaux, France.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Van Ruijssevelt
authors.forename: Pierre
authors.initials: P
authors.lastname: Smirnov
authors.forename: Anna
authors.initials: A
authors.lastname: Yudina
authors.forename: Veronique
authors.initials: V
authors.lastname: Bouchaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Voisin
authors.forename: Chrit
authors.initials: C
authors.lastname: Moonen
mesh_terms: D000165:Acridine Orange / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D051381:Rats; D013010:Sonication / Q000379:methods*; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry
chemical_list: D017304:Annexin A5; D002232:Carbocyanines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; C085925:calcein AM; C056258:N(10)-nonylacridine orange; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; C022616:thiazolyl blue; D000165:Acridine Orange