Thermosensitive Peptide-Hybrid ABC Block Copolymers Obtained by ATRP: Synthesis, Self-Assembly, and Enzymatic Degradation

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• 作者：Albert J. de Graaf ; Enrico Mastrobattista ; Tina Vermonden ; Cornelus F. van Nostrum ; Dirk T. S. Rijkers ; Rob M. J. Liskamp ; Wim E. Hennink
• 刊名：Macromolecules
• 出版年：2012
• 出版时间：January 24, 2012
• 年：2012
• 卷：45
• 期：2
• 页码：842-851
• 全文大小：383K
• 年卷期：v.45,no.2(January 24, 2012)
• ISSN：1520-5835

文摘

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鈥檚 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鈥檚 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 鈥渟hedding鈥?of the corona of the micelles which makes these systems potentially suitable for enzyme-triggered drug delivery.