Self-Assembly of Amphiphilic Copolymers with Sequence-Controlled Alternating Hydrophilic-Hydrophobic Pendant Side Chains

To design versatile ordered nanomorphologies from the alternating sequence-controlled amphiphilic copolymers, in the current work, we have investigated the self-assembly behavior of a series of alternating copolymers, prepared through the reversible addition-fragmentation chain transfer (RAFT) polymerization of methoxy poly(ethylene glycol) (mPEG) functionalized styrene (VBP) and fatty acid attached maleimide (MF) monomers. The copolymers efficiently induced self-aggregation of the pendant side chains to afford both micelle and vesicle nanostructures in aqueous medium depending on the amphiphilicity of the side chains, as evident from dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. The copolymers also induced thermoresponsive phase transition in water with lower critical solution temperatures (LCST) in the range of 69-88 degrees C depending on the mPEG side chain lengths, as determined from UV-vis spectroscopy. The hydrophobic dye and hydrophilic drug loading abilities of the synthesized copolymers were investigated using nile red and doxorubicin hydrochloride (DOX.FICI) as model compounds, respectively. The copolymers further formed reverse micelles in hexane owing to the presence of hydrophobic fatty acid pendants in the side chains, for which hexane is a good solvent. Additionally, the in vitro cytotoxicity study was performed for the synthesized alternating copolymers which revealed their nontoxic nature up to 500 mu g/mL polymer concentration. Thus, the current work represents a fundamental strategy to construct biocompatible polymeric nanostructures from amphiphilic alternating copolymers, endowing noteworthy features for potential advantages.