PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects.
There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic photodynamic therapy. Therefore, we aimed to develop covalent conjugates between the photosensitizer chlorin e6 (Ce6) and PAMAM G4.5 dendrimers. Singlet oxygen generation (SOG) efficiency and fluorescence emission were moderately affected by the covalent binding of the Ce6 to the dendrimer. Compared to free Ce6, PAMAM anchored Ce6 displays a much higher photodynamic effect, which is ascribable to better internalization in a tumor cell model. Intracellular fate and internalization pathway of our different compounds were investigated using specific inhibition conditions and confocal fluorescence microscopy. Free Ce6 was shown to enter the cells by a simple diffusion mechanism, while G4.5-Ce6-PEG internalization was dependent on the caveolae pathway, whereas G4.5-Ce6 was subjected to the clathrin-mediated endocytosis pathway. Subcellular localization of PAMAM anchored Ce6, PEGylated or not, was very similar suggesting that the nanoparticles behave similarly in the cells. As a conclusion, we have demonstrated that PEGylated G4.5 PAMAM-Ce6 dendrimers may offer effective biocompatible nanoparticles for improved photodynamic treatment in a preclinical tumor model.
Université de Lorraine, Centre de Recherche en Automatique de Nancy, Campus Sciences, Vandœuvre-lès-Nancy, France. h.lassalle@nancy.unicancer.fr and Centre National de la Recherche Scientifique, Centre de Recherche en Automatique de Nancy, France.
Estelle
E
Bastien
Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UMR 7274, CNRS, 1 rue Grandville, BP 20451, 54001 Nancy Cedex, France.
Raphaël
R
Schneider
Institut für Physik, Humboldt, Universität zu Berlin, Newtonstrasse, Berlin, Germany.
Steffen
S
Hackbarth
Université de Lorraine, Plateforme IBISA d'Imagerie et de Biophysique Cellulaire de Nancy, IMOPA7365, FR3209 BMCT, Centre National de la Recherche Scientifique, Vandœuvre-lès-Nancy, France.
Dominique
D
Dumas
Université de Lorraine, Laboratoire d'ingénierie des biomolécues (LIBio), 2 avenue de la Forêt de Haye, Vandœuvre-lès-Nancy, France.
Jordane
J
Jasniewski
Institut für Physik, Humboldt, Universität zu Berlin, Newtonstrasse, Berlin, Germany.
Beate
B
Röder
Université de Lorraine, Centre de Recherche en Automatique de Nancy, Campus Sciences, Vandœuvre-lès-Nancy, France. h.lassalle@nancy.unicancer.fr and Centre National de la Recherche Scientifique, Centre de Recherche en Automatique de Nancy, France.
Lina
L
Bezdetnaya
Université de Lorraine, Centre de Recherche en Automatique de Nancy, Campus Sciences, Vandœuvre-lès-Nancy, France. h.lassalle@nancy.unicancer.fr and Centre National de la Recherche Scientifique, Centre de Recherche en Automatique de Nancy, France.
Henri-Pierre
HP
Lassalle
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000378:metabolism
D002735:Chlorophyllides; D050091:Dendrimers; C104700:PAMAM Starburst; D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen; C062985:phytochlorin