Mechanistic Insight into Sonoporation with Ultrasound-Stimulated Polymer Microbubbles.

Autor:	Helfield BL; Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Chen X; Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Qin B; Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Watkins SC; Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Villanueva FS; Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: villanuevafs@upmc.edu.
Jazyk:	angličtina
Zdroj:	Ultrasound in medicine & biology [Ultrasound Med Biol] 2017 Nov; Vol. 43 (11), pp. 2678-2689. Date of Electronic Publication: 2017 Aug 25.
DOI:	10.1016/j.ultrasmedbio.2017.07.017
Abstrakt:	Sonoporation is emerging as a feasible, non-viral gene delivery platform for the treatment of cardiovascular disease and cancer. Despite promising results, this approach remains less efficient than viral methods. The objective of this work is to help substantiate the merit of polymeric microbubble sonoporation as a non-viral, localized cell permeation and payload delivery strategy by taking a ground-up approach to elucidating the fundamental mechanisms at play. In this study, we apply simultaneous microscopy of polymeric microbubble sonoporation over its intrinsic biophysical timescales-with sub-microsecond resolution to examine microbubble cavitation and millisecond resolution over several minutes to examine local macromolecule uptake through enhanced endothelial cell membrane permeability-bridging over six orders of magnitude in time. We quantified microbubble behavior and resulting sonoporation thresholds at transmit frequencies of 0.5, 1 and 2 MHz, and determined that sonic cracking is a necessary but insufficient condition to induce sonoporation. Further, sonoporation propensity increases with the extent of sonic cracking, namely, from partial to complete gas escape from the polymeric encapsulation. For the subset that exhibited complete gas escape from sonic cracking, a proportional relationship between the maximum projected gas area and resulting macromolecule uptake was observed. These results have revealed one aspect of polymeric bubble activity on the microsecond time scale that is associated with eliciting sonoporation in adjacent endothelial cells, and contributes toward an understanding of the physical rationale for sonoporation with polymer-encapsulated microbubble contrast agents. (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu