A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation.
In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process.
Xi
Xiaoyu
X
Institute of Acoustics, Lab of Modern Acoustics, Nanjing University, Nanjing 210093, People's Republic of China.
Yang
Fang
F
Chen
Di
D
Luo
Yi
Y
Zhang
Dong
D
Gu
Ning
N
Wu
Junru
J
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D002477:Cells / Q000166:cytology / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D005110:Extracellular Space / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D054709:Lecithins / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D014465:Ultrasonics
C115320:25-(N-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)methyl)amino)-27-norcholesterol; D005456:Fluorescent Dyes; D054709:Lecithins; D008081:Liposomes; D010714:Phosphatidylethanolamines; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D002784:Cholesterol; D009327:4-Chloro-7-nitrobenzofurazan; D016650:Fluorescein-5-isothiocyanate