Development of gene therapy of liver and bladder cancer by using nanobubbles and ultrasound

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The present research was aimed to develop a new gene therapy method of bladder and liver cancer by using nanobubbles (NBs)and ultrasound (US). The former was based on regional cancer therapy, and the later on the enhanced permeability and retention (EPR)effect. We developed acoustic liposome (NBs)(<200nm in diameter)as drug carrier and ultrasound contrast agent, dual ultrasound exposure system with high/low acoustic intensity pulses for effective delivery of fluorescent molecules and naked plasmid DNA to the bladder wall in the presence of NBs. In addition, we achieved therapeutic level by delivering tumor necrosis factor (TNF)-alpha expressing plasmid DNA to solid tumors of mice with NBs and US. Furthermore, we established a two/three-dimensional (2/3D)vascular construction method to evaluate therapeutic effects on liver cancer by using NBs and US. Our results demonstrate that the combination of these established materials and methodology can be used for a new gene therapy of bladder and liver cancer.