Thermosensitive peptide-hybrid ABC block copolymers obtained by ATRP: synthesis, self-assembly, and enzymatic degradation

de Graaf, A.J., Mastrobattista, E., Vermonden, T., van Nostrum, C., Rijkers, D.T.S., Liskamp, R.M.J. and Hennink, W.E. (2012) Thermosensitive peptide-hybrid ABC block copolymers obtained by ATRP: synthesis, self-assembly, and enzymatic degradation. Macromolecules, 45(2), pp. 842-851. (doi: 10.1021/ma2024667)

Abstract

Peptide-hybrid ABC block copolymers were synthesized by growing two different polymer chains from a native peptide using atom transfer radical polymerization (ATRP). To this end, two different ATRP initiators were coupled via orthogonal methods to the N- and C-terminus of the peptide Ser-Gly-Pro-Gln-Gly-Ile-Phe-Gly-Gln-Met-Gly, a substrate for matrix metalloproteases 2 and 9. First, a hydrophilic block of poly(oligo(ethylene glycol) methyl ether methacrylate) (pOEGMA) was polymerized from the peptide’s C-terminus. Before polymerization of the second block, the first living chain end was inactivated by substitution of its Cl-terminus with azide under mild conditions. Then, a thermosensitive block of poly(N-isopropylacrylamide) (pNIPAm) was polymerized from the peptide’s N-terminus. Well-defined polymers were obtained with good control over both block sizes. The resulting polymers self-assembled into micelles above the cloud point of the pNIPAm block. As anticipated, it was shown that the peptide linkage between the polymer blocks can be cut by a metalloprotease, leading to “shedding” of the corona of the micelles which makes these systems potentially suitable for enzyme-triggered drug delivery.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: de Graaf, A.J., Mastrobattista, E., Vermonden, T., van Nostrum, C., Rijkers, D.T.S., Liskamp, R.M.J., and Hennink, W.E.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Macromolecules
• Publisher: American Chemical Society
• ISSN: 0024-9297
• ISSN (Online): 1520-5835