Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: A real-time study - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Physical Biology Année : 2015

Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: A real-time study

Résumé

Microbubbles (MB) in combination with ultrasound (US) can enhance cell membrane permeability, and have the potential to facilitate the cellular uptake of hydrophilic molecules. However, the exact mechanism behind US- and MB-mediated intracellular delivery still remains to be fully understood. Among the proposed mechanisms are formation of transient pores and endocytosis stimulation. In our study, we investigated whether endocytosis is involved in US- and MB- mediated delivery of small molecules. Dynamic fluorescence microscopy was used to investigate the effects of endocytosis inhibitors on the pharmacokinetic parameters of US- and MB-mediated uptake of SYTOX Green, a 600 Da hydrophilic model drug. C6 rat glioma cells, together with SonoVue® microbubbles, were exposed to 1.4 MHz ultrasound waves at 0.2 MPa peak-negative pressure. Collection of the signal intensity in each individual nucleus was monitored during and after US exposure by a fibered confocal fluorescence microscope designed for real-time imaging. Exposed to ultrasound waves, C6 cells pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, showed up to a 2.5-fold significant increase of the uptake time constant, and a 1.1-fold increase with genistein, an inhibitor of caveolae-mediated endocytosis. Both inhibitors slowed down the US-mediated uptake of SYTOX Green. With C6 cells and our experimental settings, these quantitative data indicate that endocytosis plays a role in sonopermeabilization-mediated delivery of small molecules with a more predominant contribution of clathrin-mediated endocytosis.
Fichier principal
Vignette du fichier
2015_Derieppe_endocytosis.pdf (5.89 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-01159814 , version 1 (03-06-2015)

Identifiants

  • HAL Id : hal-01159814 , version 1

Citer

Marc Derieppe, Katarzyna Rojek, Jean-Michel Escoffre, Baudouin Denis de Senneville, Chrit T. W. Moonen, et al.. Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: A real-time study. Physical Biology, 2015. ⟨hal-01159814⟩

Collections

CNRS IMB INSMI
61 Consultations
31 Téléchargements

Partager

Gmail Facebook X LinkedIn More