Light-sensitive fusion between polymer-coated liposomes following physical anchoring of polymerisable polymers onto lipid bilayers by self-assembly

摘要

Delivery of therapeutics(drugs,radionuclides or genes)in vivo can be optimized when carried by a targeting delivery vehicle such as a surfactant vesicle,polymeric micelle or other polymer-coated colloidal pariculate.In the present communication,we propose a general method based on self-assembly principles,to construct lipid-polymer bilayer vesicles whose featured characteristics may be altered according to the polymer molecule used,thus be easily designed along the needs of a particular delivery application.Polymer molecules containing non-polymerizable(polypropylene)and polymerisable(methacrylate)hydrophobic groups were used to construct lipid-polymer vesicles by following two different methods of preparation.In accord with our previous findings,when both types of polymer molecules are added to pre-formed liposomes,only weak adsorption onto the lipid surface occurs.Preparation of the vesicles by pre-mixing the lipid and polymer molecules has proved essential in order to allow the hydrophobic blocks of the copolymers to participate as integral parts of the bilayer.Anchoring of a polymerisable polymer onto the lipid bilayer by hydrophobic interactions,resulted in steric stabilization of the vesicles.When UV polymerization of the bilayer-incorporated [Methyl(PEG)_2000MA] polymer was induced,inter-vesicle fusion was triggered.Direct cryo-EM imaging of fusion between the PEG-coated liposomes has been observed.Such sterically stabilised fusogenic vesicles were constructed as potential triggered-release delivery systems,responsive to a variety of external stimuli depending on the type of polymerisable,hydrophobic group in the polymer molecule.By altering the properties of the incorporated hydrophobic group,liposomes able to fuse in response to initiators milder than UV light,such as green or red light,sound,temperature,oxygen or pH can be engineered.