title: Proton-actuated membrane-destabilizing polyion complex micelles.
abstract: The efficiency of nucleic acid-based drugs is usually hampered by the fact that, following their uptake by the cell, these drugs end up in acidic organelles (i.e., endosomes/lysosomes) from which they barely escape. This work relates to the preparation and characterization of polyion complex micelles (PICM) formed by the self-assembly of three polyelectrolytes: a diblock cationic copolymer; a membranolytic, methacrylic acid copolymer; and an oligonucleotide. It is demonstrated that a synthetic membrane-active polyanion can be successfully integrated within the structure of PICM to yield well-defined, narrowly distributed micelles (30 nm) with a core/shell architecture. Besides their ability to protect the oligonucleotide against nuclease degradation, PICM partly dissociate under mildly acidic conditions, releasing chain clusters that destabilize bilayer membranes. This association/dissociation behavior illustrates the potential of these pH-sensitive PICM for the transport and efficient delivery of polyionic drugs.
authors.affiliation: Canada Research Chair in Drug Delivery, Faculty of Pharmacy, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montreal, Quebec, H3C 3J7, Canada.
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Yessine
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Dufresne
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Petereit
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008823:Micelles; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000494:pharmacology; D011522:Protons
chemical_list: D008823:Micelles; D009838:Oligodeoxyribonucleotides; D011109:Polymethacrylic Acids; D011522:Protons