Peptide-polymer bioconjugates via atom transfer radical polymerization and their solution aggregation into hybrid micro/nanospheres for dye uptake

Peptide-polymer hybrid bioconjugates containing poly(methyl methacrylate) chains attached with oligopeptide molecules were prepared by atom transfer radical polymerization (ATRP) using designed peptide-initiators. These initiators were synthesized from newly designed peptides with 2-bromoisobutyric acid via a standard coupling reaction. ATRP of methyl methacrylate was conducted using Br-terminated peptide as macroinitiator and copper(I) chloride/N,N,N′,N″,N″-pentamethyldiethylenetriamine as the catalyst system in dimethyl sulfoxide (DMSO) at an elevated temperature (90 °C). The peptide-polymer bioconjugates with controllable molecular weights and low polydispersities (PDI < 1.35) were obtained. We devised a simple solution approach in assembling the peptide-polymer bioconjugate molecules into hybrid micro/nanospheres in different organic solvents as confirmed from transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and dynamic light scattering (DLS) results. The average size of the formed hybrid micro/nanospheres decreases with the increase of the polarity of the solvent used in aggregation process. A mechanistic model was suggested for the aggregation of peptide-polymer conjugates into hybrid micro/nanospheres that correlates well with the experimental observation. The dye-loaded hybrid micro/nanospheres were simply prepared by mixing an organic dye (Rhodamine 6G) into the aggregated solution of peptide-polymer bioconjugates. The uptake of dye into the micro/nanospheres was studied by fluorescence microscopy and time-correlated single photon counting (TCSPC) techniques.