Monitoring of Insonicated Microbubble Behavior and their Effect on Sonoporation Supported Chemotherapy of Fibrosarcoma Cells

Hensel, Karin; Siepmann, Monica; Haendschke, Kathrin; Emmelmann, Sabine; Daigeler, Adrien; Hauser, Joerg; Schmitz, Georg

doi:10.1007/978-3-540-89208-3_337

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…Still, each sonoporated cell contains residuals of fluorescence intensity indicating successful drug or gene delivery. That is supported by former sonoporation studies in drug delivery and gene transfection [3,4].…”

Section: Discussionmentioning

confidence: 96%

“…This allows the non-specific uptake of molecules like fluorescent dyes, genes or drugs [2][3][4]. Large scale oscillation of nearby microbubbles (MBs) is considered to be the primary effect in sonoporation whereas MB destruction correlates with lower sonoporation efficiency [5] and increased cell damage [6].…”

Section: Abstract-ultrasound Contrast Agents Sonoporation Therapy mentioning

confidence: 99%

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Evaluation of subharmonic emission from encapsulated microbubbles as an indicator for sonoporation of cell monolayers

Hensel

Haagen

Schmitz

et al. 2009

2009 IEEE International Ultrasonics Symposium

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Sonoporation is the ultrasound induced transient opening of cell membranes. Large scale oscillation of nearby microbubbles (MBs) is considered to be the primary effect in sonoporation whereas MB destruction correlates with lower sonoporation efficiency and increased cell damage. The scale of MB oscillation in a cloud can be determined by monitoring subharmonic emission. In this study, SW480 cells are grown in Opticell containers, which are filled with a growth medium containing SonoVue MBs and propidium iodide (PI). Each container is placed in water in the focus of a single element transducer emitting 10 cycles sine-bursts at 3.3 MHz. The peak negative pressure is varied from 75 to 750 kPa. Scattered signals are recorded by a broadband transducer to monitor subharmonic-to-fundamental ratio (SFR) during therapy. A fluorescence microscope is focused on the therapy region to monitor PI fluorescence during and after acoustic excitation. PI cannot overcome intact cell membranes and changes its fluorescence properties when bound to intracellular fluid. A cell is considered sonoporated, if it reveals a sharp rise of fluorescence intensity and a subsequent decrease. A cell is considered permanently stained, if fluorescence intensity is concentrated at the cell nucleus and rises to a plateau. For maximum peak negative excitation pressure, maximum sonoporation (4.9%) and maximum permanent poration (2.8%) is observed. Correcting the number of sonoporated cells by the number of permanently stained cells, best sonoporation efficiency is achieved for the amplitude of 520 kPa. The same holds for the SFR, which significantly rises to a maximum of -26,6 dB at 520 kPa, too. The relationship of sonoporation efficiency and SFR reveals that subharmonic emission from ultrasound contrast agent is an indicator for sonoporation efficiency of cell monolayers.

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Section: Discussionmentioning

confidence: 96%

Section: Abstract-ultrasound Contrast Agents Sonoporation Therapy mentioning

confidence: 99%

Evaluation of subharmonic emission from encapsulated microbubbles as an indicator for sonoporation of cell monolayers

Hensel

Haagen

Schmitz

et al. 2009

2009 IEEE International Ultrasonics Symposium

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“…Delalande et al [ 9 ] and Fan et al [ 10 ] noted that the use of US and MB for sonoporation is being considered an emerging method for achieving localized drug and gene delivery. Owing to the variety of US conditions used and corresponding MB behavior, optimization of US conditions is essential [ 11 - 13 ]. When MB are transiently exposed to the proper US intensity, time, and duty cycle, the MB contract or collapse, simplifying delivery.…”

Section: Discussionmentioning

confidence: 99%

Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery

Yoon

Lee

2015

Ultrasonography

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Purpose:The aim of this study was to identify the optimal ultrasound (US) parameters for gene and drug delivery.Methods:In order to target SkBr3, which is a breast cancer cell overexpressing the Her2 receptor, trastuzumab (Herceptin) was used. Micobubble-nanoliposome complex (MLC) was mixed with trastuzumab and stored overnight. Finally, MLC was combined with Her2Ab. A US device equipped with a 1-MHz probe was used for delivery to the cell. Several parameters, including intensity (w/cm2), time (minutes), and duty cycle (%), were varied within a range from 1 w/cm2, 1 minute, and 20% to 2 w/cm2, 2 minutes, and 60%, respectively. A confocal laser scanning microscope (CLSM) was used to confirm the delivery of MLC to the cells after US treatment.Results:MLC with fluorescent dyes and trastuzumab was synthesized successfully. By delivering MLC with Her2Ab to cells, the targeting effect of trastuzumab with MLC was confirmed by CLSM. The cell membranes showed green (fluorescein isothiocyanate) and red (Texas red) fluorescence but treatments with MLC without Her2Ab did not show any fluorescence. Optimal conditions for US-mediated delivery were 1 or 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.9% for 1 w/cm2 and 95.7% for 2 w/cm2) for hydrophobic materials and 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.0%) for hydrophilic materials.Conclusion:The greater the strength, duty cycle, and period of US application within the tested range, the more efficiently the fluorescent contents were conveyed.

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Synergistic Effects of Sonoporation and Taurolidin/TRAIL on Apoptosis in Human Fibrosarcoma

Daigeler¹,

Chromik²,

Haendschke³

et al. 2010

Ultrasound in Medicine & Biology

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Monitoring of Insonicated Microbubble Behavior and their Effect on Sonoporation Supported Chemotherapy of Fibrosarcoma Cells

Cited by 5 publications

References 13 publications

Evaluation of subharmonic emission from encapsulated microbubbles as an indicator for sonoporation of cell monolayers

Evaluation of subharmonic emission from encapsulated microbubbles as an indicator for sonoporation of cell monolayers

Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery

Synergistic Effects of Sonoporation and Taurolidin/TRAIL on Apoptosis in Human Fibrosarcoma

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