期刊
BIOMATERIALS
卷 54, 期 -, 页码 72-86出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.03.021
关键词
Doxorubicin; Malignancy therapeutic; Oximation; pH-sensitivity; Polymer-drug conjugates; Polysaccharides
资金
- National Natural Science Foundation of China [51303174, 51233004, 51390484, 51321062, 51473165, 51203153, 51273196, 81430087, 21104076]
- Scientific Development Program of Jilin Province [20140520050JH]
Recently, chemotherapy has been one of the most important therapeutic approaches for malignant tumors. The tumor tissular or intracellular microenvironment-sensitive polymer-doxorubicin (DOX) conjugates demonstrate great potential for improved antitumor efficacy and reduced side effects. In this work, the acid-sensitive dextran-DOX conjugate (noted as Dex-O-DOX) was synthesized through the versatile efficient oximation reaction between the terminal aldehyde group of polysaccharide and the amino group in DOX in the buffer solution of sodium acetate/acetic acid. The insensitive one, i.e., Dex-b-DOX, was prepared similarly as Dex-O-DOX with a supplemented reduction reaction. The DOX release from Dex-O-DOX was pH-dependent and accelerated by the decreased pH. The efficient intracellular DOX release from Dex-O-DOX toward the human hepatoma HepG2 cells was further confirmed. Furthermore, Dex-O-DOX exhibited a closer antiproliferative activity to free DOX center dot HCl as the extension of time. More importantly, compared with Dex-b-DOX, Dex-O-DOX exhibited higher antitumor activity and lower toxicity, which were further confirmed by the systemic histological and immunohistochemical analyses. Hence, the facilely prepared smart polysaccharide-DOX conjugates, i.e., Dex-O-DOX, exhibited great potential in the clinical chemotherapy of malignancy. (C) 2015 Elsevier Ltd. All rights reserved.
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