Synthesis and self-assembly of hyperbranched multiarm copolymer peptide conjugates based on light-induced metal-free ATRP

Abstract

Light-induced metal-free atom transfer radical polymerization (ATRP) was applied in combination with the self-condensing vinyl polymerization (SCVP) to prepare hyperbranched multiarm copolymers for further peptide conjugation. Di(ethylene glycol) methyl ether methacrylate (DEGMA) was copolymerized with the inimer 2-(2-bromo-2-methylpropanoyloxy)ethyl methacrylate (BMA) through the metal-free ATRP, affording the hyperbranched polymer hPDEGMA. Further polymerization of pyridyl disulfide ethyl methacrylate (DSMA) with hPDEGMA as the macroinitiator led to the formation of the hyperbranched multiarm copolymer hPDEGMA-star-PDSMA. Glutathione as a model peptide was conjugated to hPDEGMA-star-PDSMA through the thiol-disulfide exchange reaction and the copolymer peptide conjugate hPDEGMA-star-PGS was obtained. Three hyperbranched multiarm copolymer peptide conjugates were prepared with close molecular weights but different degrees of branching (DB) and their self-assembly behaviors were studied. All three conjugates self-assembled into vesicles with narrow distributions. The conjugates with lower DB self-assembled into bilayer vesicles while the one with higher DB self-assembled into monolayer vesicles. The cysteine-modified targeting peptide HAIYPRH (T7) was also conjugated to hPDEGMA-star-PDSMA affording hPDEGMA-star-PT7. The self-assemblies of hPDEGMA-star-PT7 exhibited low toxicity towards the MCF-7 cells and could be internalized by the MCF-7 cells.