NDLI: Effects of diagnostic ultrasound parameters on molecular uptake and cell viability

Content Provider	IEEE Xplore Digital Library
Author	van Wamel, A. Bouakaz, A. ten Cate, F. de Jong, N.
Copyright Year	2002
Description	Author affiliation: Thoraxcentre, Erasmus MC, Rotterdam, Netherlands (van Wamel, A.; Bouakaz, A.; ten Cate, F.; de Jong, N.)
Abstract	The success of drug or gene delivery is limited by the inability of those components to cross biological barriers like the cell membrane. Ultrasound (US) has shown to increase cell membrane permeability in a process known as sonoporation. So far most investigations have used acoustic settings such as continuous wave or high intensity focused ultrasound, which are well far from the diagnostic range. Since a few years now, other studies used US waves with diagnostic conditions but in combination with contrast bubbles. The purpose of our study is to determine the effect of US alone on cell uptake using diagnostic parameters, and to correlate the sonoporation mechanism on the different diagnostic conditions. Monolayers of CHO cells, fixed on a membrane, are used whereby Texas-red labeled dextran (10 nm) is used as a marker molecule. The experimental parameters were: acoustic pressure 0.2-1.4 MPa P_, pulse length (10/spl mu/s-15/spl mu/s), duty cycle (0-0.75%), total exposure time (0-6 minutes) and addition of contrast microbubbles. Transmitted frequency was 1 MHz and the temperature was kept constant at 37/spl deg/C. The control cells showed no molecular uptake. For exposure times <30 s, sonoporation increased with increased MI. For exposure times > 30, sonoporation increased transiently with increasing MI reaching a maximum at MI 0.7. Using MI between 0.2-0.7, maximum sonoporation was reached after 2 minutes of exposure. Using ultrasound with MI 1.4 during 30 sec gave the highest molecular uptake (33%) but also very high cell lysis (40%). Under stronger diagnostic conditions (MI 1.4 and total exposure time above 2 min), lysis occurred up to 65% and almost no cells were sonoporated. Increasing repetition rate resulted in a higher cell lysis and very low sonoporation. Addition of contrast microbubbles resulted in a higher cell lysis but not in a higher molecular uptake. Significant molecular uptake can be induced by diagnostic pulsed US without using contrast bubbles. For pressures >1.4 MPa and exposure time >30s, (repetition rate 0.01 sec and 0.1% duty cycle) the US treatment results in cell-lysis. Both molecular uptake and cell viability strongly depend on total exposure time, applied MI, repetition rate, duty cycle, and addition of contrast microbubbles. Addition of contrast microbubbles enhanced the ultrasound effects.
Sponsorship	Ultransonics Ferroelectr., & Frequency Control Soc
Starting Page	1419
Ending Page	1422
File Size	67592
Page Count	4
File Format	PDF
ISBN	0780375823
ISSN	10510117
DOI	10.1109/ULTSYM.2002.1192562
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2002-10-08
Publisher Place	Germany
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Ultrasonic imaging Cells (biology) Biomembranes Drugs Acoustic pulses Frequency Temperature Acoustic transducers Permeability Acoustic waves
Content Type	Text
Resource Type	Article

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