Mannosylated Poly(ethylene oxide)-b-Poly(epsilon-caprolactone) Diblock Copolymers:Synthesis,Characterization,and Interaction with a Bacterial Lectin

摘要

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(e-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ethylene oxide and epsilon-caprolactone,followed by the coupling of a reactive mannose derivative to the PEO chain end.The anionic polymerization of ethylene oxide was first initiated by potassium 2-dimethylaminoethanolate.The ring-opening polymerization of epsilon-caprolactone was then initiated by the omega-hydroxy end-group of PEO previously converted into an A1 alkoxide.Finally,the saccharidic end-group was attached by quaternization of the tertiary amine alpha-end-group of the PEO-b-PCL with a brominated mannose derivative.The copolymer was fully characterized in terms of chemical composition and purity by high-resolution NMR spectroscopy and size exclusion chromatography.Furthermore,measurements with a pendant drop tensiometer showed that both the mannosylated copolymer and the non-mannosylated counterpart significantly decreased the dichloromethane/water interfacial tension.Moreover,these amphiphilic copolymers formed monodisperse spherical micelles in water with an average diameter of ~11 nm as measured by dynamic light scattering and cryo-transmission electron microscopy.The availability of mannose as a specific recognition site at the surface of the micelles was proved by isothermal titration microcalorimetry (ITC),using the BclA lectin (from Burkholderia cenocepacia),which interacts selectively with a-D-mannopy-ranoside derivatives.The thermodynamic parameters of the lectin/mannose interaction were extracted from the ITC data.These colloidal systems have great potential for drug targeting and vaccine delivery systems.