title: Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery.
abstract: OBJECTIVE
  The aim of this study was to identify the optimal ultrasound (US) parameters for gene and drug delivery.
  
  
  METHODS
  In order to target SkBr3, which is a breast cancer cell overexpressing the Her2 receptor, trastuzumab (Herceptin) was used. Micobubble-nanoliposome complex (MLC) was mixed with trastuzumab and stored overnight. Finally, MLC was combined with Her2Ab. A US device equipped with a 1-MHz probe was used for delivery to the cell. Several parameters, including intensity (w/cm(2)), time (minutes), and duty cycle (%), were varied within a range from 1 w/cm(2), 1 minute, and 20% to 2 w/cm(2), 2 minutes, and 60%, respectively. A confocal laser scanning microscope (CLSM) was used to confirm the delivery of MLC to the cells after US treatment.
  
  
  RESULTS
  MLC with fluorescent dyes and trastuzumab was synthesized successfully. By delivering MLC with Her2Ab to cells, the targeting effect of trastuzumab with MLC was confirmed by CLSM. The cell membranes showed green (fluorescein isothiocyanate) and red (Texas red) fluorescence but treatments with MLC without Her2Ab did not show any fluorescence. Optimal conditions for US-mediated delivery were 1 or 2 w/cm(2), 2 minutes, and 60% (uptake ratio, 95.9% for 1 w/cm(2) and 95.7% for 2 w/cm(2)) for hydrophobic materials and 2 w/cm(2), 2 minutes, and 60% (uptake ratio, 95.0%) for hydrophilic materials.
  
  
  CONCLUSIONS
  The greater the strength, duty cycle, and period of US application within the tested range, the more efficiently the fluorescent contents were conveyed.
authors.affiliation: Program in Nano Science and Technology, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Korea ; Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Young Il
authors.identifier: 0000-0001-9957-4896
authors.initials: YI
authors.lastname: Yoon
authors.affiliation: Department of Applied Bioscience, CHA University, Seongnam, Korea.
authors.forename: Tae-Jong
authors.identifier: 0000-0002-0809-8319
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: Program in Nano Science and Technology, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Korea ; Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Hak Jong
authors.identifier: 0000-0003-0858-7873
authors.initials: HJ
authors.lastname: Lee
keywords: Liposomes; Microbubbles; Therapy, image-guided; Ultrasound