Drug release by direct jump from poly(ethylene-glycol-b-ε-caprolactone) nano-vector to cell membrane

Ugo Till (1) , Laure Gibot (2) , Anne-Françoise Mingotaud (1, 3) , Jérôme Ehrhart (1) , Luc Wasungu (2) , Christophe Mingotaud (1, 3) , Jean-Pierre Souchard (1, 3) , Alix Poinso (1) , Marie-Pierre Rols (2) , Frédéric Violleau (4) , Patricia Vicendo (1, 3)

1 IMRCP - Interactions moléculaires et réactivité chimique et photochimique
2 IPBS - Institut de pharmacologie et de biologie structurale
3 IMRCP - IDeAS - IMRCP - Interfaces Dynamiques et Assemblages Stimulables
4 CAI - Chimie Agro-Industrielle

Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers. This study showed that the cellular uptake and the phototoxicity of loaded Pheo-a are ten times higher than those of the free drug and revealed a very low cellular penetration of the fluorescence-labeled micelles. Neither loaded nor free Pheo-a displayed the same cellular localization as the labeled micelles. These results imply that the drug entered the cells without its carrier and probably without a disruption, as suggested by their stability in cell culture medium. These data allowed us to propose that Pheo-a directly migrates from the micelle to the cell without disruption of the vector. This mechanism will be discussed.

Mots clés: copolymer; nanoparticle; pheophorbide-a; polymer micelles; cellular penetration; uptake mechanism

Mots clés: copolymère; nanoparticule; mécanisme d'absorption; voie de penetration; micelle

Domaines: Génie chimique

Ugo Till, Laure Gibot, Anne-Françoise Mingotaud, Jérôme Ehrhart, Luc Wasungu, et al.. Drug release by direct jump from poly(ethylene-glycol-b-ε-caprolactone) nano-vector to cell membrane. Molecules, 2016, 21 (12), 15 p. ⟨10.3390/molecules21121643⟩. ⟨hal-01594383⟩