Gene Transfection Enhanced by Ultrasound Exposure Combined with Drug Treatment

Ultrasound (US) has been explored as a means of non-viral gene delivery. US can penetrate tissues and focus its energy to non-superficial targets within a small volume. These properties lead to non-invasive and site-specific cellular effects that promote gene delivery. US-mediated gene transfection has been studied both in vitro and in vivo. Several key challenges still exist in this method, including the heterogenic bioeffects, unclear mechanisms and unknown cellular pathways influenced by US exposure.

We hypothesize that US facilitates gene transfection as well as regulates the intracellular processes, and the regulation of these intracellular processes with addition of chemicals can enhance the transfection efficiency mediated by US exposure. In the present study, gene expression among DU145 human prostate cancer cells after US-mediated transfection was analyzed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. Genes associated with cell cycle were found to be associated with successful transfection, such as Gadd45α (growth arrest and DNA-damage inducible, alpha) and Topoisomerase IIα. Drug treatments suggested by the microarray analysis were used with US exposure to regulate the corresponding intracellular processes. Mechanistically, we found treatment with drugs that regulated cell cycle (e.g. taxol) showed the potential to increase transfection efficiency mediated by US. This provides the proof of principle that regulation of intracellular prosesses using drugs could enhance US-mediated gene transfection.