Intracellular Delivery of Bleomycin by Combined Application of Electroporation and Sonoporation in Vitro.
In this study, we aimed to determine whether the combination of electroporation (EP) and ultrasound (US) waves (sonoporation) can result in an increased intracellular delivery of anticancer drug bleomycin. CHO cells were treated with electric pulses (1 or 8 high voltage pulses of 800 or 1200 V/cm, 100 μs or 1 low voltage pulse of 100 or 250 V/cm, 100 ms) and with 880 kHz US of 320 or 500 kPa peak negative pressure, 100 % duty cycle, applied for 2 s in the presence or absence of exogenously added contrast agent microbubbles. Various sequential or simultaneous combinations of EP and sonoporation were used. The results of the study showed that i) sequential treatment of cells by EP and sonoporation enhanced bleomycin electrosonotransfer at the reduced energy of electric field and US; ii) sequential combination of EP and sonoporation induced a summation effect which at some conditions was more prominent when the cells were treated first by EP and then by sonoporation; iii) the most efficient intracellular delivery of bleomycin was achieved by the simultaneous application of cell EP and sonoporation resulting in percentage of reversibly porated cells above the summation level; and iv) compared with sequential application of EP and sonoporation, simultaneous use of electric pulses and US increased cell viability in the absence of bleomycin.
Biophysical research group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos 8, 44404, Kaunas, Lithuania.
Mindaugas
M
Tamošiūnas
Vectorology and Anticancer Therapeutics, UMR 8203, Univ. Paris-Sud Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France.
Lluis M
LM
Mir
Department of Physical Medicine & Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan.
Wen-Shiang
WS
Chen
Institute of Atomic Physics and Spectroscopy, University of Latvia, Rīga, Latvia.
Alexey
A
Lihachev
Biophysical research group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos 8, 44404, Kaunas, Lithuania.
Mindaugas
M
Venslauskas
Biophysical research group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos 8, 44404, Kaunas, Lithuania. s.satkauskas@gmf.vdu.lt.
Saulius
S
Šatkauskas
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001761:Bleomycin / Q000008:administration & dosage*; D016466:CHO Cells; D002470:Cell Survival; D003412:Cricetulus; D016503:Drug Delivery Systems; D018274:Electroporation / Q000379:methods; D045423:Microbubbles; D000069453:Ultrasonic Waves
D000970:Antineoplastic Agents; D001761:Bleomycin
Drug delivery; Electroporation; Electrosonoporation; Microbubbles; Sonoporation; Ultrasound