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

本研究旨在开发一种利用纳米气泡（NBs）和超声（US）联合治疗膀胱癌和肝癌的新方法。前者是基于局部肿瘤治疗，后者是基于增强渗透性和潴留（EPR）效应。我们开发了声学脂质体（NBs）（直径<200nm）作为药物载体和超声造影剂，以及在NBs存在下将荧光分子和裸质粒DNA有效递送到膀胱壁的高/低声强脉冲双超声暴露系统。此外，我们通过将表达肿瘤坏死因子(TNF)- α的质粒DNA传递给NBs和US小鼠实体瘤，达到了治疗水平。此外，我们建立了二/三维（2/3D）血管构建方法来评价NBs和US对肝癌的治疗效果。我们的结果表明，这些已建立的材料和方法的组合可以用于新的基因治疗膀胱癌和肝癌。

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.