Plasma membrane poration induced by ultrasound exposure: implication for drug delivery.
Sonoporation, in the presence of ultrasound contrast agents (UCA), is a technique that permits the transfer of drugs, including genes, into cells. In this study, the size of the pores created by ultrasound application, and the duration of pore opening, have been characterized via indirect molecular probing and microscopic observation. Internalization of molecules with diameters up to 37 nm was efficient and generally well-tolerated; on the other hand, confocal microscopy revealed that 75 nm particles entered only a few cells when sonoporation was applied. In general, the larger the species to internalize, the poorer the transfer. Direct visualization of pores following insonification, using scanning electron microscopy, was hampered by the presence of numerous villi on the surface of the cells employed (MAT B III), and by the short duration of pore opening. Clearer observations of porated regions were possible using red blood cells. This research (i) confirms that sonoporation is a means with which to achieve macromolecule delivery into cells, and (ii) characterizes in some detail the phenomenon of ultrasound induction of transient pores in the cell membrane.
Mehier-Humbert
Sophie
S
University of Geneva, School of Pharmacy and Biopharmacy, CH-1211 Geneva 4, Switzerland. sophie.mehier@brg.bracco.com
Bettinger
Thierry
T
Yan
Feng
F
Guy
Richard H
RH
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000648:ultrastructure*; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems / Q000379:methods*; D018613:Microscopy, Confocal; D016062:Porosity; D051381:Rats; D014465:Ultrasonics