Charge-Shifting Copolymers of 2-( N , N -Dimethylamino)Ethyl Acrylate and 2-Hydroxyethyl Acrylate via RAFT Polymerization: Balancing the Charge Content and Biological Response

High Resolution Image Download MS PowerPoint Slide Synthetic polycations are key components for engineering polyelectrolyte complexes with wide-ranging biomedical potential. However, the high cytotoxicity of fully charged polycations remains a major limitation for clinical applications. To address this challenge, we report on polycations derived from the cationic monomer 2-( N,N -dimethylaminoethyl) acrylate (DMAEA), which gradually loses charge through hydrolysis, thereby reducing their charge density over time. The overall charge fraction (from 100% to 20%) was further controlled through copolymerization with the neutral comonomer 2-hydroxyethyl acrylate (HEA). The selected conditions of reversible addition–fragmentation chain transfer (RAFT) copolymerization, specifically protonation of DMAEA with trifluoroacetic acid to mask its tertiary amino groups, enabled a precise control over the characteristics of the copolymers (termed D/H) up to 75% conversions, with close agreement between theoretical and experimental molecular weights up to 100 000 g/mol, consistently low dispersities (