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Encapsidation of RNA–Polyelectrolyte Complexes with Amphiphilic Block Copolymers: Toward a New Self-Assembly Route
journal contribution
posted on 2012-12-12, 00:00 authored by Laurent Bui, Scarlette Abbou, Emmanuel Ibarboure, Nicolas Guidolin, Cathy Staedel, Jean-Jacques Toulmé, Sébastien Lecommandoux, Christophe SchatzAmphiphilic block copolymers are molecules composed of
hydrophilic
and hydrophobic segments having the capacity to spontaneously self-assemble
into a variety of supramolecular structures like micelles and vesicles.
Here, we propose an original way to self-assemble amphiphilic block
copolymers into a supported bilayer membrane for defined coating of
nanoparticles. The heart of the method rests on a change of the amphiphilicity
of the copolymer that can be turned off and on by varying the polarity
of the solvent. In this condition, the assembly process can take advantage
of specific molecular interactions in both organic solvent and water.
While the concept potentially could be applied to any type of charged
substrates, we focus our interest on the design of a new type of polymer
assembly mimicking the virus morphology. A capsid-like shell of glycoprotein-mimic
amphiphilic block copolymer was self-assembled around a positively
charged complex of siRNA and polyethyleneimine. The process requires
two steps. Block copolymers first interact with the complexes dispersed
in DMSO through electrostatic interactions. Next, the increase of
the water content in the medium triggers the hydrophobic effect and
the concomitant self-assembly of free block copolymer molecules into
a bilayer membrane at the complex surface. The higher gene silencing
activity of the copolymer-modified complexes over the complexes alone
shows the potential of this new type of nanoconstructs for biological
applications, especially for the delivery of therapeutic biomolecules.