Star‐shaped polypeptide/glycopolymer biohybrids: Synthesis, self‐assembly, biomolecular recognition, and controlled drug release behavior

Star‐shaped polypeptide/glycopolymer biohybrids composed of poly(γ‐ benzyl L‐glutamate) and poly(D‐gluconamidoethyl methacrylate), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring‐opening polymerization of γ‐benzyl‐L‐glutamate N‐carboxyanhydride and the direct atom transfer radical polymerization of unprotected D‐gluconamidoethyl methacrylate glycomonomer. These biohybrids were characterized in detail by means of FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X‐ray diffraction. Independent of weight fraction of hydrophilic glycopolymer segment, the biohybrids self‐assembled into large spherical micelles in aqueous solution, which had a helical polypeptide core surrounded by a multivalent glycopolymer shell. The deprotected poly(L‐glutamate)/glycopolymer hybrid exhibited a pH‐sensitive self‐assembly behavior, and the average size of the nanoparticles decreased gradually over the aqueous pH value. Moreover, whatever these biohybrids existed in unimolecular level or glycopolymer‐surfaced nanoparticles, they had specific biomolecular recognition with Concanavalin A compared with bovine serum albumin. Furthermore, star‐shaped biohybrids showed a higher doxorubicin loading efficiency and longer drug‐release time than linear analogues. This potentially provides a platform for fabricating targeted anticancer drug delivery system and studying glycoprotein functions in vitro.