Synthesis and characterization of biodegradable pH and reduction dual-sensitive polymeric micelles for doxorubicin delivery
Yanfeng Chu
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorHuan Yu
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorYingying Ma
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorYunti Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorWeihai Chen
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorGuangyan Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Hubei Provincial Key Laboratory of Green Materials for Light Industry, Hubei University of Technology, Wuhan, 430068 People's Republic of China
Search for more papers by this authorHua Wei
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, Washington, 98195
Search for more papers by this authorXianzheng Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorRenxi Zhuo
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorCorresponding Author
Xulin Jiang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Correspondence to: X. Jiang (E-mail: [email protected])Search for more papers by this authorYanfeng Chu
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorHuan Yu
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorYingying Ma
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorYunti Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorWeihai Chen
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorGuangyan Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Hubei Provincial Key Laboratory of Green Materials for Light Industry, Hubei University of Technology, Wuhan, 430068 People's Republic of China
Search for more papers by this authorHua Wei
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, Washington, 98195
Search for more papers by this authorXianzheng Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorRenxi Zhuo
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Search for more papers by this authorCorresponding Author
Xulin Jiang
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072 People's Republic of China
Correspondence to: X. Jiang (E-mail: [email protected])Search for more papers by this authorABSTRACT
Novel pH and reduction dual-sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy-poly(ethylene glycol)-b-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl) imidazole-l-aspartamide)] [mPEG-SS-P(BLA-co-APILA), MPBA] synthesized by a combination of ring-opening polymerization and side-chain reaction. The pH/reduction-responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX-loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX-loaded micelles showed retarded drug release in phosphate-buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX-loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual-responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1771–1780
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