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

Sachiko Horie, Yukiko Watanabe, Rui Chen, Shiro Mori, Yasuhiro Matsumura, Tetsuya Kodama

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1867-1875
Number of pages9
JournalUltrasound in Medicine and Biology
Issue number11
Publication statusPublished - 2010 Nov


  • Acoustic liposome
  • Bladder cancer
  • Drug delivery system
  • Localized gene delivery
  • Nanobubble
  • Ultrasound

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics


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