Gene therapy progress and prospects: Ultrasound for gene transfer

Sonoluminescence and acoustic emission spectra at different stages of cavitation zone development

“…This interest is motivated by the promising results obtained during the study of ultrasonically induced biological effects including, I) enhanced cell membrane permeability which improves the delivery of small compounds, macromolecules and other therapeutics into cells and tissues, i.e. sonoporation [6][7][8][9]; II) DNA-mediated transfection [10,11]; III) tumour growth reduction [12,13], and IV) the activation of specific compounds triggering antitumor or antimicrobial activity [14][15][16][17]. It is believed that cavitation plays an important role in these bio-effects.…”

“…It is believed that cavitation plays an important role in these bio-effects. Three types of ultrasound action on biological cells have been identified [6][7][8][9][10][11][12][13][14][15][16][17][18]; damping viability, reversible cell damage (sonoporation) and irreversible damage/cytotoxicity. It is possible that these types of action derive from the different properties that cavitation displays under different conditions, meaning that the monitoring and control of cavitation is therefore an important factor in the successful use of ultrasound in medicine and biology.…”

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

“…Our initial selection of ultrasound parameters was based on previous studies without flow, which have shown that higher acoustic pressures increase not only the desired trans-membrane 10 delivery efficiency, but also the unwanted cellular damage (Brayman et al, 1999;Qiu et al, 2012). Studies have also shown that inertial cavitation is responsible for the decreased cell viability (Newman and Bettinger, 2007). Yet there have been reports of successful trans-membrane delivery while maintaining cell viability, but this has been limited to a very small percentage of the total sonicated cell population (Lammertink et al, 2014;Qiu 15 et al, 2012Qiu 15 et al, , 2010.…”

“…Transient cavitation describes short-lived phenomena, which can be caused by fragmentation of the shell, dissolution of the core gas, or other mechanisms (Apfel, 1997;Chomas et al, 2001;Newman and Bettinger, 2007). One cause of a transient response is 20 inertial cavitation, which arises when the rarefactional phase of the ultrasound pulse results in a radial expansion followed by a violent collapse dominated by the inertia of the surrounding liquid medium (Church and Carstensen, 2001;Flynn, 1982).…”

“…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.…”