Biomimetic pH/redox dual stimuli‐responsive zwitterionic polymer block poly(L‐histidine) micelles for intracellular delivery of doxorubicin into tumor cells |
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| Authors: | Johnson V. John Saji Uthaman Rimesh Augustine Kamali Manickavasagam Lekshmi In‐Kyu Park Il Kim |
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| Affiliation: | 1. BK21 PLUS Center for Advanced Chemical Technology, Department of Polymer Science and Engineering, Pusan National University, Busan, Republic of Korea;2. Department of Biomedical Science, BK21 PLUS Centre for Creative Biomedical Scientists, Chonnam National University Medical School, Republic of Korea |
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| Abstract: | A series of pH/redox dual stimuli‐responsive poly(2‐methacryloyloxyethyl phosphorylcholine)25‐block‐poly(l ‐histidine)n (p[MPC])25‐b‐p[His]n, n = 20, 35, 50, and 75) copolymers consisting of a pH‐responsive p(His)n block and a biocompatible phospholipid analog p(MPC) block connected by a redox‐responsive disulfide linker have been synthesized. The block copolymers are self‐assembled into uniform micelles (～100 nm) in which doxorubicin (Dox) is efficiently encapsulated. The in vitro release profile shows an enhanced release of Dox at low pH (5.0) in 10 mM glutathione (GSH). The in vitro cell viability assays performed using various cell lines show that the blank hybrid micelles have no acute or intrinsic toxicity. A pH‐dependent cytotoxicity is observed with the Dox‐loaded micelles, especially at pH 5.0. Moreover, confocal microscopy images and flow cytometry results show the pH‐dependent cellular uptake of Dox‐loaded micelles. Therefore, the Dox‐loaded micelles can be considered a good candidate for cancer therapy. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2061–2070 |
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| Keywords: | biopolymers block copolymers drug delivery peptides responsive polymers |
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