Synthesis of polypeptide bearing 1,4-dithiane pendants for ROS-responsive drug release |
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| Affiliation: | 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. University of Science and Technology of China, Hefei 230026, China;3. Department of Chemistry, Northeast Normal University, Changchun 130021, China;4. State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China;5. Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China;1. Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA;2. Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA;3. Department of Pharmacokinetics & Drug Metabolism RNA, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA;4. Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA;1. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, China;2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China;3. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, 130012, China;4. Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China;1. Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany;2. Graduate School of Materials Science in Mainz, Staudingerweg 9, 55128 Mainz, Germany;3. Institute of Physical Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany |
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| Abstract: | Stimuli-responsive polypeptides have been intensively investigated for controlled drug release, owing to their favorable biocompatibility and biodegradability. In this work, we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species (ROS)-responsive drug release. The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization (ROP) of 1,4-dithian-substituted l-glutamate N-carboxyanhydride (DTG-NCA) monomer using an amino-terminated poly(ethylene glycol) methyl ether (mPEG-NH2) as the macromolecular initiator. The resultant block copolymer, mPEG-b-PDTG, could self-assemble into uniform micelles in aqueous medium owing to its amphiphilic structure. Then, the H2O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering (DLS), FT-IR and turbidimetric assay. It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles. Furthermore, the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug. MTT assay also proved that mPEG-b-PDTG was non-toxic in B16F10 and L929 cells. Therefore, such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery. |
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| Keywords: | Polypeptides ROS-responsive Self-assembly Thioether Drug release |
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