Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery.
Fiche publication
Date publication
mai 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KLYMCHENKO Andrey
Tous les auteurs :
Sobot D, Mura S, Yesylevskyy SO, Dalbin L, Cayre F, Bort G, Mougin J, Desmaële D, Lepetre-Mouelhi S, Pieters G, Andreiuk B, Klymchenko AS, Paul JL, Ramseyer C, Couvreur P
Lien Pubmed
Résumé
Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. Interestingly, not only SQGem but also other squalene derivatives interact similarly with lipoproteins while such interaction is not observed with liposomes. The conjugation to squalene represents a versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins.
Mots clés
A549 Cells, Animals, Calorimetry, Cell Line, Cell Line, Tumor, Cholesterol, chemistry, Deoxycytidine, analogs & derivatives, Drug Delivery Systems, Fluorescence Resonance Energy Transfer, Humans, Ligands, Lipoproteins, chemistry, Liposomes, chemistry, MCF-7 Cells, Nanoparticles, chemistry, Neoplasms, drug therapy, Rats, Receptors, LDL, metabolism, Squalene, chemistry
Référence
Nat Commun. 2017 05 30;8:15678