Construction of PEG-based amphiphilic brush polymers bearing hydrophobic poly(lactic acid) side chains via successive RAFT polymerization and ROP

A series of well-defined amphiphilic brush polymers containing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(lactic acid) segments was synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization, ring opening polymerization (ROP), and the graftingfrom strategy. tert-Butyl 2-((4-hydroxybutanoyloxy)methyl)acrylate (tBHBMA) monomer containing a ROP initiation group (-OH) was first RAFT block copolymerized using a PEG-based chain transfer agent to form two well-defined PEG-b-PtBHBMA diblock copolymers (M-w/M-n <= 1.10) bearing pendant hydroxyls in every repeated unit of PtBHBMA segment. Both diblock copolymers directly initiated ROP of lactide by the pendant hydroxyls to provide well-defined poly(ethylene glycol)-b-(poly(tert-butyl acrylate)-g-poly (lactic acid)) (PEG-b-(PtBA-g-PLA)) brush polymers (M-w/M-n = 1.16) without post-polymerization functionality transformation. The target well-defined poly(ethylene glycol)-b-(polyacrylic acid)-g-poly(lactic acid) (PEG-b-(PAA-g-PLA))amphiphilic brush polymers were achieved by the selective acidolysis of hydrophobic PtBA backbone (tert-butyoxycarbonyls) into hydrophilic PAA backbone (carboxyls) using trifluoroacetic acid. PEG-b-(PAA-g-PLA) brush polymers could self-assemble into spheres with a size of ca. 70-110 nm in aqueous media as evidenced by DLS and TEM. The drug (doxorubicin) loading ability of PEG-b-(PAA-g-PLA) brush polymers was investigated preliminarily by measuring the in vitro cell (SMMC-7721 and SH-SY5Y) viabilities, which showed higher cytotoxicity compared to free DOX.