Synthesis of Aldehyde Functionalized and Degradable Block Copolymers and Their Bioconjugation

A well-defined degradable and aldehyde-functionalized amphiphilic block copolymer PEO-b-poly(VBA-co-BMDO) with narrow molecular weight distribution (M-w/M-n < 1. 20) was synthesized via reversible addition-fragmentation chain transfer (RAFT) copolymerization of 4-vinylbenzaldehyde (VBA) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) using PEO-DDMAT as chain transfer agent and benzoyl peroxide (BPO) as initiator at 80 degrees C in 2-butanone. Copolymers with variable amounts of BMDO or VBA units could be obtained just by changing the feed composition. The obtained amphiphilic block copolymers were found to be hydrolytically degradable due to the main-chain polyester structure. Low cytotoxicity against L929 cells was observed at polymer concentration up to 1. 0 mg mL(-1), indicating that amphiphilic block copolymer PEO-b-poly(VBA-co-BMDO) exhibits good biocompatibility. The highly reactive aldehyde functions in the synthesized amphiphilic block copolymer could provide the key intermediates to conjugate biomolecules, and the availability of the amphiphilic block copolymer to conjugate bioactive molecules was confirmed via aldehyde-aminooy click reaction with an aminooxy model drug, aminooxy functionalized cholesterol (H2NO-Chol). The successful conjugate formation was demonstrated by GPC and H-1-NMR analyses. Self-assemblies in water of the amphiphilic block copolymer PEO-b-poly(VBA-co-BMDO) and its bioconjugate were also investigated by dynamic light scattering (DLS) and scanning electron microscopy (SEM) measurements. The conjugates of PEO-b-poly(VBA-co-BMDO) with cholesterol could self-assemble into spherical micelles in aqueous solution with size in the range of 70 similar to 110 nm. These results suggested that the amphiphilic copolymer PEO-b-poly(VBA-co-BMDO) would be useful as a versatile polymer scaffold for bioconjugating.