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Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy

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Abstract

Purpose

Transport across the plasma membrane is a critical step of drug delivery for weakly permeable compounds with intracellular mode of action. The purpose of this study is to demonstrate real-time monitoring of ultrasound (US)-mediated cell-impermeable model drug uptake with fibered confocal fluorescence microscopy (FCFM).

Procedures

An in vitro setup was designed to combine a mono-element US transducer, a cell chamber with a monolayer of tumor cells together with SonoVue microbubbles, and a FCFM system. The cell-impermeable intercalating dye, SYTOX Green, was used to monitor US-mediated uptake.

Results

The majority of the cell population showed fluorescence signal enhancement 10 s after US onset. The mean rate constant k of signal enhancement was calculated to be 0.23 ± 0.04 min−1.

Conclusions

Feasibility of real-time monitoring of US-mediated intracellular delivery by FCFM has been demonstrated. The method allowed quantitative assessment of model drug uptake, holding great promise for further local drug delivery studies.

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Acknowledgments

We are grateful to Dr. J.R. Cazalets and colleagues (INCIA UMR 5287/University Bordeaux 2, France) for letting us use their cell culture facility. This study was supported by EU project SonoDrugs (FP7-NMP4-LA-2008-213706), ERC project 268906 “Sound Pharma”, and Foundation InNaBioSanté—project ULTRAFITT.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory for Molecular and Functional Imaging: From Physiology to Therapy, FRE 3313–CNRS and University Bordeaux Segalen, 146, rue Léo Saignat, Case 117, 33076, Bordeaux cedex, France

    Marc Derieppe, Anna Yudina, Matthieu Lepetit-Coiffé, Baudouin Denis de Senneville & Chrit Moonen

  2. Imaging Division, University Medical Center Utrecht, Heidelberglaan 100, P.O. Box 85500,, 3508 GA, Utrecht, Netherlands

    Marc Derieppe, Anna Yudina, Clemens Bos & Chrit Moonen

  3. Institut de Mathématiques de Bordeaux, UMR 5251–CNRS–Université Bordeaux 1–INRIA, Bordeaux, France

    Baudouin Denis de Senneville

Authors
  1. Marc Derieppe
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  2. Anna Yudina
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  3. Matthieu Lepetit-Coiffé
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  4. Baudouin Denis de Senneville
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  5. Clemens Bos
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  6. Chrit Moonen
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Corresponding author

Correspondence to Chrit Moonen.

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Derieppe, M., Yudina, A., Lepetit-Coiffé, M. et al. Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy. Mol Imaging Biol 15, 3–11 (2013). https://doi.org/10.1007/s11307-012-0568-9

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  • DOI: https://doi.org/10.1007/s11307-012-0568-9

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