RAFT synthesis of reactive multifunctional triblock-copolymers for polyplex formation

Abstract

Reversible addition–fragmentation chain transfer polymerization with a low-temperature initiator can be used to synthesize multifunctional block copolymers for polyplex formation. Utilizing three methacrylate monomers (triethylene glycol methyl ether methacrylate (MEO3MA), pyridyldisulfideethyl methacrylate (PDSM), N,N-dimethylethylenediamine methacrylate (DMAEMA)) and an azide bearing chain transfer agent for polymerization, the resulting triblock-copolymers possess two orthogonally reactive functionalities (a block with reactive disulfide side chains and an azide end-group) and two additional functional blocks for i) solubilization and ii) polyplex formation. Thereby, the MEO3MA block provides solubility in aqueous media and the DMAEMA block, having a tertiary amine in the side chain, allows polyplex formation with polyanionic biomacromolecules like DNA or RNA. Due to the reactive disulfide block the polyplexes can be (reversibly) crosslinked with dithiols. Because of the manifold of possibilities to modify the pDNApolyplexes, this polymers system is an interesting candidate for active-targeting and codelivery approaches.