title: Ultrasound activated nano-encapsulated targeted drug delivery and tumour cell poration.
abstract: BACKGROUND
  Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano--encapsulated drug carriers.The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS).
  
  
  METHODS
  Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37-55°C for 2-10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15.
  
  
  RESULTS
  We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis. DISCUSSION AND FUTURE WORK: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system.
authors.affiliation: Institute of Medical Science and Technology, University of Dundee, Dundee, UK. d.gourevich@dundee.ac.uk
authors.forename: Dana
authors.initials: D
authors.lastname: Gourevich
authors.forename: Bjoern
authors.initials: B
authors.lastname: Gerold
authors.forename: Fabian
authors.initials: F
authors.lastname: Arditti
authors.forename: Doudou
authors.initials: D
authors.lastname: Xu
authors.forename: Dun
authors.initials: D
authors.lastname: Liu
authors.forename: Alex
authors.initials: A
authors.lastname: Volovick
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Yoav
authors.initials: Y
authors.lastname: Medan
authors.forename: Jallal
authors.initials: J
authors.lastname: Gnaim
authors.forename: Paul
authors.initials: P
authors.lastname: Prentice
authors.forename: Sandy
authors.initials: S
authors.lastname: Cochran
authors.forename: Andreas
authors.initials: A
authors.lastname: Melzer
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D007624:KB Cells; D053769:Nanocapsules / Q000737:chemistry*; D014465:Ultrasonics / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D004317:Doxorubicin