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

Abstract : 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.
Type de document :
Article dans une revue
Physical Biology, Institute of Physics: Hybrid Open Access, 2015
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-01159814
Contributeur : Baudouin Denis de Senneville <>
Soumis le : mercredi 3 juin 2015 - 18:45:12
Dernière modification le : jeudi 19 octobre 2017 - 09:50:01

Fichier

2015_Derieppe_endocytosis.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

  • HAL Id : hal-01159814, version 1

Collections

IMB

Citation

Marc Derieppe, Katarzyna Rojek, Jean-Michel Escoffre, Baudouin Denis de Senneville, Chrit Moonen, et al.. Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: A real-time study. Physical Biology, Institute of Physics: Hybrid Open Access, 2015. 〈hal-01159814〉

Partager

Métriques

Consultations de
la notice

74

Téléchargements du document

3