title: Nanoparticles Formed by Acoustic Destruction of Microbubbles and Their Utilization for Imaging and Effects on Therapy by High Intensity Focused Ultrasound.
abstract: This work reports that when PEG-lipid-shelled microbubbles with fluorocarbon interior (C4F10, C5F12, or C6F14) are subjected to ultrasound pulses, they produce metastable, fluid-filled nanoparticles that can be re-imaged upon administration of HIFU. The nanoparticles produced by destruction of the microbubbles (MBNPs) are of 150 nm average diameter and can be re-imaged for up to an hour after creation for C4F10, and for at least one day for C5F12. The active species were found to be fluid (gas or liquid) filled nanoparticles rather than lipid debris. The acoustic droplet vaporization threshold of the nanoparticles was found to vary with the vapor pressure of the encapsulated fluorocarbon, and integrated image brightness was found to increase dramatically when the temperature was raised above the normal boiling point of the fluorocarbon. Finally, the vaporization threshold decreases in serum as compared to buffer, and administration of HIFU to the nanoparticles caused breast cancer cells to completely detach from their culture substrate. This work demonstrates a new functionality of microbubbles that could serve as a platform technology for ultrasound-based theranostics.
authors.affiliation: Department of Chemical and Biological Engineering. University of Colorado Boulder. Boulder, CO 80303.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Blum
authors.affiliation: Department of Chemical and Biological Engineering. University of Colorado Boulder. Boulder, CO 80303.
authors.forename: Adem
authors.initials: A
authors.lastname: Yildirim
authors.affiliation: Department of Mechanical Engineering, University of Colorado Boulder. Boulder, CO 80309.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Chattaraj
authors.affiliation: Department of Chemical and Biological Engineering. University of Colorado Boulder. Boulder, CO 80303.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Goodwin
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000378:metabolism; D005466:Fluorocarbons / Q000378:metabolism*; D006801:Humans; D045423:Microbubbles; D053758:Nanoparticles; D013696:Temperature; D000068936:Theranostic Nanomedicine / Q000379:methods; D014464:Ultrasonic Therapy / Q000379:methods*; D014463:Ultrasonography / Q000379:methods*; D014835:Volatilization
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons
keywords: microbubbles; ultrasound pulses