Proton-Actuated Membrane-Destabilizing Polyion Complex Micelles
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- 作者：Marie-André ; e Yessine ; Marie-Hé ; lè ; ne Dufresne ; Christian Meier ; Hans-Ulrich Petereit ; Jean-Christophe Leroux
- 刊名：Bioconjugate Chemistry
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：18
- 期：3
- 页码：1010 - 1014
- 全文大小：357K
- 年卷期：v.18,no.3(May 2007)
- ISSN：1520-4812
文摘
The efficiency of nucleic acid-based drugs is usually hampered by the fact that, following their uptake by thecell, these drugs end up in acidic organelles (i.e., endosomes/lysosomes) from which they barely escape. Thiswork 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 integratedwithin the structure of PICM to yield well-defined, narrowly distributed micelles (30 nm) with a core/shellarchitecture. Besides their ability to protect the oligonucleotide against nuclease degradation, PICM partly dissociateunder 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 deliveryof polyionic drugs.