Frequency-Dependent Evaluation of the Role of Definity in Producing Sonoporation of Chinese Hamster Ovary Cells
2011; Wiley; Volume: 30; Issue: 1 Linguagem: Inglês
10.7863/jum.2011.30.1.61
ISSN1550-9613
AutoresMonica M. Forbes, Ryan L. Steinberg, William D. O’Brien,
Tópico(s)Photoacoustic and Ultrasonic Imaging
ResumoJournal of Ultrasound in MedicineVolume 30, Issue 1 p. 61-69 Original Research Frequency-Dependent Evaluation of the Role of Definity in Producing Sonoporation of Chinese Hamster Ovary Cells Monica M. Forbes PhD, Monica M. Forbes PhD Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USASearch for more papers by this authorRyan L. Steinberg BS, Ryan L. Steinberg BS Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USASearch for more papers by this authorWilliam D. O'Brien Jr PhD, Corresponding Author William D. O'Brien Jr PhD [email protected] Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USA Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois USAAddress correspondence to William D. O'Brien, Jr, PhD, ECE Department, UIUC, 405 N Mathews, Urbana, IL 61801 USA.Search for more papers by this author Monica M. Forbes PhD, Monica M. Forbes PhD Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USASearch for more papers by this authorRyan L. Steinberg BS, Ryan L. Steinberg BS Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USASearch for more papers by this authorWilliam D. O'Brien Jr PhD, Corresponding Author William D. O'Brien Jr PhD [email protected] Department of Bio-engineering University of Illinois at Urbana-Champaign, Urbana, Illinois USA Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois USAAddress correspondence to William D. O'Brien, Jr, PhD, ECE Department, UIUC, 405 N Mathews, Urbana, IL 61801 USA.Search for more papers by this author First published: 01 January 2011 https://doi.org/10.7863/jum.2011.30.1.61Citations: 32Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Objectives Sonoporation uses ultrasound (US) and ultrasound contrast agents (UCAs) to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds non-invasively into specific target cells. The objective of this study was to elucidate the biophysical mechanism of sonoporation, specifically the role of UCAs as well as exposure frequency. The inertial cavitation (IC) thresholds of the lipid-shelled octafluoropropane UCA were directly compared to the levels of generated sonoporation to determine the involvement of UCAs in producing sonoporation. Methods Chinese hamster ovary cells were exposed as a monolayer in a solution of the UCA, 500,000-Da fluorescein isothiocyanate-dextran, and phosphate-buffered saline to 30 seconds of pulsed US (pulse duration, 5 cycles; pulse repetition frequency, 10 Hz) at 3 frequencies (0.92, 3.2, and 5.6 MHz). The peak rarefactional pressure (Pr) was varied over a range from 4 kPa to 4.1 MPa, and 5 to 7 independent replicates were performed at each pressure. Results The experimental observations demonstrated that IC was likely not the physical mechanism for sonoporation. Sonoporation activity was observed at pressure levels below the threshold for IC of the UCA (1.27 ± 0.32 MPa at 0.92 MHz, 0.84 ± 0.19 MPa at 3.2 MHz, and 2.57 ± 0.26 MPa at 5.6 MHz) for all 3 frequencies examined. The Pr values at which the peak sonoporation activity occurred were 1.4 MPa at 0.92 MHz, 0.25 MPa at 3.2 MHz, and 2.3 MPa at 5.6 MHz. The UCA collapse thresholds followed a similar trend. A 1-way analysis of variance test confirmed that sonoporation activity differed among the 3 frequencies examined (P = 10−8). Conclusions These results thus suggest that sonoporation is related to linear and/or nonlinear oscillation of the UCA occurring at pressure levels below the IC threshold. References 1Datta S, Coussios CC, Ammi AY, Mast TD, de Courten-Myers GM, Holland CK. Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent. Ultrasound Med Biol 2008; 34: 1421–1433. 2Maxwell AD, Cain CA, Duryea AP, Yuan L, Gurm HS, Xu Z. 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