title: Tumor transfection after systemic injection of DNA lipid nanocapsules.
abstract: With the goal of generating an efficient vector for systemic gene delivery, a new kind of nanocarrier consisting of lipid nanocapsules encapsulating DOTAP/DOPE lipoplexes (DNA LNCs) was pegylated by the post-insertion of amphiphilic and flexible polymers. The aim of this surface modification was to create a long-circulating vector, able to circulate in the blood stream and efficient in transfecting tumoral cells after passive targeting by enhanced permeability and retention effect (EPR effect). PEG conformation, electrostatic features, and hydrophylicity are known to be important factors able to influence the pharmacokinetic behaviour of vectors. In this context, the surface structure characteristics of the newly pegylated DNA LNCs were studied by measuring electrophoretic mobility as a function of ionic strength in order to establish a correlation between surface properties and in vivo performance of the vector. Finally, thanks to this PEGylation, gene expression was measured up to 84-fold higher in tumor compared to other tested organs after intravenous injection. The present results indicate that PEGylated DNA LNCs are promising carriers for an efficient cancer gene therapy.
authors.affiliation: Inserm U646, Université d'Angers, 10 rue André Boquel, F-49100 Angers, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Morille
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bastiat
authors.forename: Bruno
authors.initials: B
authors.lastname: Pitard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D057809:HEK293 Cells; D006801:Humans; D007267:Injections; D008055:Lipids / Q000008:administration & dosage*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage*; D009369:Neoplasms / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
chemical_list: D008055:Lipids; D053769:Nanocapsules; D011092:Polyethylene Glycols; D004247:DNA