The correlation between acoustic cavitation and sonoporation involved in ultrasound-mediated DNA transfection with polyethylenimine (PEI) in vitro

Enhancement of Non-Invasive Trans-Membrane Drug Delivery Using Ultrasound and Microbubbles During Physiologically Relevant Flow

“…More recently, GFP reporter plasmids were delivered to HEK294 cells with an efficiency of up 10 to 80% (Tlaxca et al, 2010). A similar delivery rate was achieved at high pressures in the DNA transfection of MCF-7 cells (Qiu et al, 2010). However, high delivery rates were accomplished at the expense of cell viability, with extended cell death being observed at high pressure sonication (P pk-neg > 500kPa); in contrast, low acoustic pressures (P pk-neg < 100kPa pk-neg ) were proved to be safer but resulted in transfection efficiency below 15% 15 (Qiu et al, 2012).…”

“…Proposed routes of molecular delivery include the formation of short-lived pores in the membrane, also known as sonoporation (Yu and Xu, 2014), and endocytosis (Geers et al, 2011;van Wamel et al, 2006). In addition, increased transmembrane delivery efficiency is associated with increased damage and cell death (Qiu et al, 2012(Qiu et al, , 2010, and this efficacy-safety trade-off has limited the technology's 15 development and hence it remains unutilized in the clinic as a drug delivery tool.…”

“…The different types of acoustic cavitation have been demonstrated to produce diverse cellular effects (Fan et al, 2014;Mehier-Humbert et al, 2005;Qiu et al, 2010). First, it has been shown that the interaction between the microbubble oscillation and the cell membrane can produce short-lived pores that allow drug uptake.…”

“…These pores are up to 1 μm in size and have been shown to reseal within seconds (Hu et al, 2013;Newman 5 and Bettinger, 2007;Qiu et al, 2010;Zhou et al, 2009), minutes (Schlicher et al, 2006) or even hours (Zhao et al, 2008). Inertial cavitation produces higher rates of intracellular delivery than stable cavitation (Fan et al, 2013;Karshafian et al, 2009;Park et al, 2011;Qiu et al, 2010), however the cellular membrane is more likely to be disrupted and that influences cell viability (Newman and Bettinger, 2007). Furthermore, at diagnostic 10 frequencies and acoustic pressures, endothelial damage can occur when contrast agents are under ultrasound exposure, due to the generation of inertial cavitation.…”

“…Severe cell damage was also associated with the acoustic pressure of the applied pulses. As the acoustic pressure increases, damage increases in a generally linear fashion (Brayman et al, 1999;Qiu et al, 2010). Thus, an ultrasound pulse sequence must be designed to fulfill the requirement of both minimum cell damage and maximum desired bioeffect.…”