Journal
MOLECULAR IMAGING AND BIOLOGY
Volume 15, Issue 1, Pages 3-11Publisher
SPRINGER
DOI: 10.1007/s11307-012-0568-9
Keywords
Drug delivery; Biological barrier; Plasma membrane permeabilization; Ultrasound bioeffects; Fibered confocal fluorescence microscopy; Pharmacokinetic parameters; SYTOX Green; US-mediated drug delivery
Funding
- EU [FP7-NMP4-LA-2008-213706]
- ERC [268906]
- Foundation InNaBioSante
- European Research Council (ERC) [268906] Funding Source: European Research Council (ERC)
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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). 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. 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). 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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