Elucidating the mechanisms behind sonoporation with adeno-associated virus-loaded microbubbles.
Microbubbles are Food and Drug Administration (FDA) approved contrast agents for ultrasound imaging. It has been reported that applying ultrasound on drug-loaded microbubbles facilitates drug uptake by cells, due to so-named sonoporation. However, the biophysics behind sonoporation are not fully understood. It is believed that sonoporation results in a "direct" delivery of drugs in the cytoplasm of cells, though it has been suggested as well that sonoporation facilitates endocytosis which would improve the internalization of drugs by cells. To get a better understanding of sonoporation, this study reports on the ultrasound assisted delivery of adeno-associated virus (AAV) loaded on the surface of microbubbles. AAVs rely on endocytosis for efficient transduction of cells and are, consequently, an elegant tool to evaluate whether endocytosis is involved in ultrasound-induced sonoporation. Applying ultrasound on AAV-loaded microbubbles clearly improved the internalization of AAVs by cells, though transduction of the cells did not occur, indicating that by sonoporation substances become directly delivered in the cytosol of cells.
Ghent Research Group on Nanomedicines, Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium.
Bart
B
Geers
Ine
I
Lentacker
Angelika
A
Alonso
Niek N
NN
Sanders
Joseph
J
Demeester
Stephen
S
Meairs
Stefaan C
SC
De Smedt
D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D000229:Dependovirus; D016503:Drug Delivery Systems; D011992:Endosomes / Q000000981:diagnostic imaging / Q000378:metabolism; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D045423:Microbubbles; D018613:Microscopy, Confocal; D008954:Models, Biological; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D013010:Sonication; D014464:Ultrasonic Therapy; D014463:Ultrasonography
D003287:Contrast Media; D011092:Polyethylene Glycols