Smart Polymeric Nanocarriers of Met-enkephalin

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• 作者：Roza Szweda ; Barbara Trzebicka ; Andrzej Dworak ; Lukasz Otulakowski ; Dominik Kosowski ; Justyna Hertlein ; Emi Haladjova ; Stanislav Rangelov ; Dawid Szweda
• 刊名：Biomacromolecules
• 出版年：2016
• 出版时间：August 8, 2016
• 年：2016
• 卷：17
• 期：8
• 页码：2691-2700
• 全文大小：631K
• 年卷期：0
• ISSN：1526-4602

文摘

This study describes a novel approach to polymeric nanocarriers of the therapeutic peptide met-enkephalin based on the aggregation of thermoresponsive polymers. Thermoresponsive bioconjugate poly((di(ethylene glycol) monomethyl ether methacrylate)-ran-(oligo(ethylene glycol) monomethyl ether methacrylate) is synthesized by AGET ATRP using modified met-enkephalin as a macroinitiator. The abrupt heating of bioconjugate water solution leads to the self-assembly of bioconjugate chains and the formation of mesoglobules of controlled sizes. Mesoglobules formed by bioconjugates are stabilized by coating with cross-linked two-layer shell via nucleated radical polymerization of N-isopropylacrylamide using a degradable cross-linker. The targeting peptide RGD, containing the fluorescence marker carboxyfluorescein, is linked to a nanocarrier during the formation of the outer shell layer. In the presence of glutathione, the whole shell is completely degradable and the met-enkephalin conjugate is released. It is anticipated that precisely engineered nanoparticles protecting their cargo will emerge as the next-generation platform for cancer therapy and many other biomedical applications.