Selective Clinical Ultrasound Signals Mediate Differential Gene Transfer and Expression in Two Human Prostate Cancer Cell Lines: LnCap and PC-3

In vitro and in vivo transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 is enhanced by focused ultrasound

“…Ultrasound cell/tissue interaction mechanisms include nonthermal mechanical effects from high positive and negative ultrasound pressure waves, shear forces, and transient cavitation, defined as the existence of small bubbles. 27 Several groups have proposed the use of ultrasound either as lithotripter shock waves in vitro 23 and in vivo 24 or as nonfocused sinusoidal lowpressure ultrasound waves in vitro [20][21][22] as a method to enhance the transfection of plasmid DNA. Most authors considered cavitation as the dominant mechanism to induce transfection.…”

“…[27][28][29][30][31] A burst frequency of 100 Hz was used, since this frequency was reported to produce the optimal transfection efficiency for cells in culture including two human prostate cancer cell lines. 21,29 Furthermore, we varied the pressure amplitude, referring to the positive pressure amplitude in the focus of the undisturbed sound field in water (0.1 to 5 MPa) and the total sonication time (10 s to 10 min). The pressure amplitude of 1 MPa, the total sonication time of 3 min, and the burst length of 4 ms were chosen for the further experiments because this combination had shown the optimal ratio of stimulation and cell viability.…”

“…17 Other in vitro reports indicate that genes can be transferred into mammalian cells 18 and plants 19 by ultrasound cleaning and sterilization equipment. In recent in vitro experiments sinusoidal ultrasound [20][21][22] and lithotripter shock waves were used to mediate plasmid DNA transfer into mammalian cells. 23 More recently, a report about in vivo transfection of melanoma cells by lithotripter shock waves has been encouraging.…”

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery

“…The optimal ultrasound parameters for transfection such as sonication time, pressure, frequency, averaged intensity, and cavitation dose have not been systematically characterized. 5,6,14,16,17,19,20,32 Sinusoidal focused ultrasound transfection can be applied at an intensity level without substantial side effects, and, unlike a number of viral gene transfer vectors, multiple, repeated ultrasound transfection applications are possible. Further improvements of efficiency are therefore possible, including the use of adjuncts such as liposomal sheltering of plasmids.…”

“…Accordingly, ultrasonic shockwaves 11 and low-dose sinusoidal ultrasound have been shown to permeabilize cell membranes and mediate the transfer of proteins, 12 and molecules such as dextranes into cells. 13 It has also been demonstrated that ultrasound enhances the transfer of plasmid DNA into cells in culture, [14][15][16][17][18][19] skeletal muscle in vivo, 20,21 and experimental tumors in vivo. 22 A wide range of ultrasonic waves have been used to augment gene transfer such as low-level diagnostic ultrasound, 20 ultrasonic shockwaves 22 and HIFU.…”