Real-time Assessment of Ultrasound-mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2012 Jun 19

PMID 22707046

Citations 10

Authors

Marc Derieppe

Anna Yudina

Matthieu Lepetit-Coiffe

Baudouin Denis de Senneville

Clemens Bos

Chrit Moonen

Affiliations

Soon will be listed here.

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.

Citing Articles

Intracellular Pharmacokinetics of Activated Drugs in a Prodrug-Enzyme-Ultrasound System: Evaluations on ZD2767P+CPG2+US.

Yu T, Li X, Yu T, Chen M, Sun Y, Ran R ACS Med Chem Lett. 2024; 15(5):739-745.

PMID: 38746880 PMC: 11089658. DOI: 10.1021/acsmedchemlett.4c00071.

Assessment of Intratumoral Doxorubicin Penetration after Mild Hyperthermia-Mediated Release from Thermosensitive Liposomes.

Derieppe M, Escoffre J, Denis de Senneville B, van Houtum Q, Rijbroek A, van der Wurff-Jacobs K Contrast Media Mol Imaging. 2019; 2019:2645928.

PMID: 30956626 PMC: 6431439. DOI: 10.1155/2019/2645928.

Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques.

Todorova B, Salabert N, Tricot S, Boisgard R, Rathaux M, Le Grand R Contrast Media Mol Imaging. 2017; 2017:3127908.

PMID: 29097915 PMC: 5612736. DOI: 10.1155/2017/3127908.

Dynamic Fluorescence Microscopy of Cellular Uptake of Intercalating Model Drugs by Ultrasound-Activated Microbubbles.

Lammertink B, Deckers R, Derieppe M, De Cock I, Lentacker I, Storm G Mol Imaging Biol. 2017; 19(5):683-693.

PMID: 28213832 PMC: 5574961. DOI: 10.1007/s11307-016-1042-x.

Real-time monitoring of magnetic drug targeting using fibered confocal fluorescence microscopy.

Bai J, Wang J, Mei K, Al-Jamal W, Al-Jamal K J Control Release. 2016; 244(Pt B):240-246.

PMID: 27449744 PMC: 5176088. DOI: 10.1016/j.jconrel.2016.07.026.

References

Staruch R, Chopra R, Hynynen K . Localised drug release using MRI-controlled focused ultrasound hyperthermia. Int J Hyperthermia. 2010; 27(2):156-71. DOI: 10.3109/02656736.2010.518198. View

Yudina A, Lepetit-Coiffe M, Moonen C . Evaluation of the temporal window for drug delivery following ultrasound-mediated membrane permeability enhancement. Mol Imaging Biol. 2010; 13(2):239-49. DOI: 10.1007/s11307-010-0346-5. View

Al-Gubory K, Houdebine L . In vivo imaging of green fluorescent protein-expressing cells in transgenic animals using fibred confocal fluorescence microscopy. Eur J Cell Biol. 2006; 85(8):837-45. DOI: 10.1016/j.ejcb.2006.03.007. View

Deckers R, Yudina A, Cardoit L, Moonen C . A fluorescent chromophore TOTO-3 as a 'smart probe' for the assessment of ultrasound-mediated local drug delivery in vivo. Contrast Media Mol Imaging. 2011; 6(4):267-74. DOI: 10.1002/cmmi.426. View

Hallow D, Mahajan A, Prausnitz M . Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries. J Control Release. 2007; 118(3):285-93. PMC: 1892790. DOI: 10.1016/j.jconrel.2006.12.029. View

Ter Haar G . Therapeutic applications of ultrasound. Prog Biophys Mol Biol. 2006; 93(1-3):111-29. DOI: 10.1016/j.pbiomolbio.2006.07.005. View

Mitragotri S . Healing sound: the use of ultrasound in drug delivery and other therapeutic applications. Nat Rev Drug Discov. 2005; 4(3):255-60. DOI: 10.1038/nrd1662. View

Lehr H, Leunig M, Menger M, Nolte D, Messmer K . Dorsal skinfold chamber technique for intravital microscopy in nude mice. Am J Pathol. 1993; 143(4):1055-62. PMC: 1887078. View

Luciani A, Wilhelm C, Bruneval P, Cunin P, Autret G, Rahmouni A . Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver. Eur Radiol. 2009; 19(5):1087-96. DOI: 10.1007/s00330-008-1262-9. View

10.

Ogawa K, Tachibana K, Uchida T, Tai T, Yamashita N, Tsujita N . High-resolution scanning electron microscopic evaluation of cell-membrane porosity by ultrasound. Med Electron Microsc. 2002; 34(4):249-53. DOI: 10.1007/s007950100022. View

11.

White N, Errington R . Fluorescence techniques for drug delivery research: theory and practice. Adv Drug Deliv Rev. 2004; 57(1):17-42. DOI: 10.1016/j.addr.2004.08.003. View

12.

Horowitz S . The permeability of the amphibian oocyte nucleus, in situ. J Cell Biol. 1972; 54(3):609-25. PMC: 2200292. DOI: 10.1083/jcb.54.3.609. View

13.

Sundaram J, Mellein B, Mitragotri S . An experimental and theoretical analysis of ultrasound-induced permeabilization of cell membranes. Biophys J. 2003; 84(5):3087-101. PMC: 1302870. DOI: 10.1016/S0006-3495(03)70034-4. View

14.

Mehier-Humbert S, Bettinger T, Yan F, Guy R . Plasma membrane poration induced by ultrasound exposure: implication for drug delivery. J Control Release. 2005; 104(1):213-22. DOI: 10.1016/j.jconrel.2005.01.007. View

15.

Sung K, Richards-Kortum R, Follen M, Malpica A, Liang C, Descour M . Fiber optic confocal reflectance microscopy: a new real-time technique to view nuclear morphology in cervical squamous epithelium in vivo. Opt Express. 2009; 11(24):3171-81. DOI: 10.1364/oe.11.003171. View

16.

Lin K, Maricevich M, Bardeesy N, Weissleder R, Mahmood U . In vivo quantitative microvasculature phenotype imaging of healthy and malignant tissues using a fiber-optic confocal laser microprobe. Transl Oncol. 2008; 1(2):84-94. PMC: 2510813. DOI: 10.1593/tlo.08118. View

17.

Greis C . Technology overview: SonoVue (Bracco, Milan). Eur Radiol. 2005; 14 Suppl 8:P11-5. View

18.

Dreher M, Liu W, Michelich C, Dewhirst M, Yuan F, Chilkoti A . Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006; 98(5):335-44. DOI: 10.1093/jnci/djj070. View

19.

Yeh E, Tong A, Lenihan D, Yusuf S, Swafford J, Champion C . Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004; 109(25):3122-31. DOI: 10.1161/01.CIR.0000133187.74800.B9. View

20.

van Wamel A, Kooiman K, Harteveld M, Emmer M, Ten Cate F, Versluis M . Vibrating microbubbles poking individual cells: drug transfer into cells via sonoporation. J Control Release. 2006; 112(2):149-55. DOI: 10.1016/j.jconrel.2006.02.007. View