Approach to peptide decorated micelles via RAFT polymerization

Pyridyldisulfide (PDS) functionalized telechelic polymers of oligo(ethyleneglycol) acrylate (PEG-A) and their amphiphilic triblock copolymers with styrene (St) were synthesized directly by reversible addition- fragmentation chain transfer (RAFT) polymerization using a new bifunctional RAFT agent, S,S-bis[a,a -dimethyl-a?-(2-pyridyl disulfide) ethyl acetate] trithiocarbonate (BDPET). The homopolymerization of PEG-A was found to be well controlled using BDPET (PDI <1.2). The ABA triblock copolymers poly(PEG-A)-6-poly(St)-6-poly(PEG-A) with narrow molecular weight distribution (PDI <1.25) were synthesized using poly(PEG-A) as a macroRAFT agent. UV-vis spectroscopic analysis revealed that 85 mol of poly(PEG-A) and 78 mol of poly(PEG-A)-b-poly(St)-b-poly(PEG-A) retained PDS end group functionality. Micelles were observed to form from poly(PEG-A)-b-poly(St)-b-poly(PEG-A). The presence of PDS groups within the micelle corona was evidenced by UV-vis spectroscopy and fluorescence spectroscopy. The PDS groups within the corona were then used to functionalize the micelles with a thiol group bearing model peptide, reduced glutathione, and a thiol modified fluorophore, rhodamine B, under mild reaction conditions. UV-vis and fluorescence spectrocopies revealed that approximately 80 PDS groups from the amphiphilic copolymer were tethered within the micelle coronas and accessible to glutathione and fluorophore attachment.