Development of localized gene delivery using a dual-intensity ultrasound system in the bladder

Abstract

A dual-intensity ultrasound system (DIUS) using nanobubbles offers opportunities for localized gene delivery. This system consists of low-/high-ultrasound intensities. The bladder is a balloon-shaped closed organ in which the behavior of nanobubbles can be controlled spatially and temporally by ultrasound exposure. We hypothesized that when a DIUS with nanobubbles was used, low-intensity ultrasound would direct nanobubbles to targeted cells in the bladder, whereas high-intensity ultrasound intensity would collapse nanobubbles and increase cell membrane permeability, facilitating entry of exogenous molecules into proximate cells. A high-frequency ultrasound imaging system characterized movement and fragmentation of nanobubbles in the bladder. Confocal microscopy revealed that fluorescent molecules were delivered in the localized bladder wall, whereas histochemical examination indicated that the molecular transfer efficiency depended on the acoustic energy. A bioluminescence imaging system showed luciferase plasmid DNA was actually transfected in the bladder wall and subsequent transfection depended on acoustic energy. These findings indicate that delivery of exogenous molecules in the bladder using this approach results in high localization of molecular delivery, facilitating gene therapy for bladder cancer.