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Abstract

En route towards improved delivery systems for targeted chemotherapy,} we propose a straightforward approach for the hydrophobic modification of the acrylamide N-(2-Hydroxyethyl)acrylamide (HEAm). An ethyl or benzyl group was introduced via a hydrolytically sensitive carbonate ester yielding HEAm-EC and HEAm-BC{,} respectively. Block copolymers of HEAm{,} respectively PEG and HEAm-EC or HEAm-BC were successfully synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization{,} obtaining a library of well-defined block copolymers with different degrees of polymerization (DP). To further explore the versatility of our approach in terms of polymer synthesis{,} self-assembly{,} drug solubilization and in vitro cell interaction{,} polyethylene glycol (PEG) and polyHEAm as hydrophilic polymer blocks were compared. The block copolymers formed micellar nanoparticles (10–100 nm) in PBS and could efficiently solubilize hydrophobic dyes and anti-cancer drugs. Benzyl carbonate ester side chains increased micellar stability and drug loading capacity. Moreover{,} PEG as hydrophilic block showed in comparison to HEAm more promising results concerning both colloidal stability and drug loading capacity. Confocal microscopy showed that the micelles could efficiently deliver a hydrophobic dye inside the cells. Finally{,} we also demonstrated efficient formulation of the anti-cancer drug paclitaxel with an in vitro cancer cell killing performance comparable or even better than the two commercial PTX nanoformulations Abraxane and Genexol-PM at equal drug dose. In conclusion{, modification of HEAm through carbonate linkages offers a versatile platform for the design of degradable polymers with potential for biomedical applications.