title: Anionic pH-sensitive pegylated lipoplexes to deliver DNA to tumors.
abstract: Anionic pegylated lipoplexes have been prepared from the combined formulation of cationic lipoplexes and pegylated anionic liposomes. To this end, two original (bis- and tetra-) carboxylated cholesterol derivatives have been synthesised. Titration of the particle surface charge was realised to determine the ratio between anionic and cationic lipids that would give pH-sensitive complexes. This ratio has been optimised to form particles sensitive to pH change in the range 5.5-6.5. Compaction of DNA into these newly formed anionic complexes was checked by DNA accessibility to picogreen and DNA electrophoresis on an agarose gel. Gene expression of the formulated gene was similar for the cationic formulation taken as a control and the anionic formulations prepared. The pH-sensitive properties of these formulations was shown in vitro using bafilomycin, a vacuolar H(+)ATPase inhibitor. The efficiency of the new formulations to deliver DNA to the tumor was compared with cholesteryl hemisuccinate (CHEMS) formulations. The tetracarboxylated compound gave the most efficient formulations for tumor delivery in vivo.
authors.affiliation: Unité de Pharmacologie Chimique et Génétique, CNRS, UMR 8151, Paris Cedex F-75270, France. Nathalie.Mignet@univ-paris5.fr
authors.forename: N
authors.initials: N
authors.lastname: Mignet
authors.forename: C
authors.initials: C
authors.lastname: Richard
authors.forename: J
authors.initials: J
authors.lastname: Seguin
authors.forename: C
authors.initials: C
authors.lastname: Largeau
authors.forename: M
authors.initials: M
authors.lastname: Bessodes
authors.forename: D
authors.initials: D
authors.lastname: Scherman
mesh_terms: D000818:Animals; D000838:Anions; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D002788:Cholesterol Esters / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000838:Anions; D002264:Carboxylic Acids; D002788:Cholesterol Esters; D008081:Liposomes; D011092:Polyethylene Glycols; D004247:DNA; D002784:Cholesterol; C013440:cholesteryl succinate