Pulsed High-Intensity Focused Ultrasound Enhances Systemic Administration of Naked DNA in Squamous Cell Carcinoma Model: Initial Experience

Abstract

Local exposure to pulsed high-intensity focused ultrasound in tumors can enhance the delivery and expression of systemically injected naked DNA.

Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

“…pFUS exposures similar to those employed in the present study have been used to non-invasively and nondestructively enhance the delivery of a variety of systemically administered agents in murine solid tumors including plasmid DNA (Dittmar et al, 2005), small molecules (Poff et al, 2008), nanoparticles (Frenkel et al, 2006), and monoclonal antibodies (Khaibullina et al, 2008). More recently, in a study in the murine skeletal muscle, the same exposures were shown to enhance the delivery of both systemically and locally administered nanoparticles (Hancock et al, 2009).…”

“…Although changes in peak displacements were not observed, significant increases in the time required for the tissue to return back to its initial, pre-treatment state was found in all the treated tumors. Previous studies in a variety of tumors models, including HNSCC, have shown that pFUS exposures do not cause damage to the tissue (Dittmar et al, 2005;Frenkel et al, 2006;Khaibullina et al, 2008). The increase in the relaxation time in the treated tumors, which essentially indicates a reduction in tissue elasticity, must have then occurred from a decrease in the amount of fluid in the tumors.…”

“…One million cells were implanted subcutaneously in the unilateral flanks of female C3H mice (25 g) as previously described (Dittmar et al, 2005). For all studies, tumors were grown to a size of 250 mm 3 and then randomized into groups.…”

“…Finally, the samples were stained with hematoxylin-eosin (H&E), dehydrated in graded alcohol, cleared in xylene, and then cover-slipped. Slides were viewed using a microscope (Axioplan 2; Carl Zeiss MicroImaging, NY) at 100Â and representative digital images were captured (Dittmar et al, 2005).…”

“…As a result, temperature elevations may be just a few degrees Celsius (and hence non-destructive), allowing for more delicate, non-thermal mechanisms to occur (Frenkel, 2008). pFUS exposures have demonstrated the ability to noninvasively enhance the delivery of a variety of systemically administered agents to solid tumors, including small molecules (Poff et al, 2008), plasmid DNA (Dittmar et al, 2005), monoclonal antibodies (Khaibullina et al, 2008), and nanoparticles (Dittmar et al, 2005;Frenkel et al, 2006). More recently, these exposures were shown to enhance the distribution of locally administered nanoparticles in skeletal muscle (Hancock et al, 2009).…”