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Design of Environment-Sensitive Supramolecular Assemblies for Intracellular Drug Delivery: Polymeric Micelles that are Responsive to Intracellular pH Change

Authors

  • Younsoo Bae,

    1. Department of Material Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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  • Shigeto Fukushima,

    1. Department of Material Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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  • Atsushi Harada,

    1. Department of Material Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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  • Kazunori Kataoka Prof. Dr.

    1. Department of Material Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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  • This work is financially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST). The authors acknowledge the National Cancer Center Research Institute, Japan, for supplying a human small cell lung cancer cell line SBC-3. Y.B. acknowledges financial support from the Japanese Monbusho's scholarship program.

Abstract

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Drug smuggling: Micelles made up of block copolymers and the anticancer drug adriamycin (ADR), which is linked to the polymer by a pH-sensitive linker, have been prepared (see picture). Treatment of cancer cells with the micelles shows that the micelles are transported into the cell by endocytosis, thus bypassing the cell-membrane transporters. In the cell, the decrease in pH value triggers the release of the ADR, which retains its cytotoxic effect. The released ADR fluoresces which allows its localization within the cells to be detected.

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