期刊
CARBOHYDRATE POLYMERS
卷 155, 期 -, 页码 407-415出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2016.08.072
关键词
Carboxymethyl chitosan; Micelles; Cisplatin; Doxorubicin; Combination therapy; Drug delivery
资金
- National Nature Science Foundation of China [51273156, 31300791]
- key project of scientific research of Education Department, Hubei Province [D20161901]
The delivery of combination chemotherapy by nanoscale platforms has been demonstrated to enhance cancer treatment in the clinic. Cisplatin (CDDP)-crosslinked, glutathione-sensitive, tumor-targeting micelles based on carboxymethyl chitosan were designed for synergistic cisplatin-doxorubicin (DOX) combination chemotherapy. In our study, DOX was conjugated to carboxymethyl chitosan through a disulfide bond, which was structurally characterized by H-1 NMR. The micelles formed by self-assembly were spherical, with the mean diameter of 274 nm. The in vitro release studies revealed that the micelles were highly glutathione-sensitive. Cytotoxicity analysis demonstrated that the cisplatin-crosslinked micelles loaded with DOX exhibited enhanced therapeutic efficacy compared with the DOX-loaded nanoparticles, free DOX, and free CDDP. Cellular uptake and intracellular release revealed that the cisplatin-crosslinked micelles loaded with DOX could efficiently deliver and release DOX into the cancer cells. These results clearly indicate that tumor-targeting and glutathione-sensitive micelles provide means for combination drug delivery in cancer treatment. (C) 2016 Published by Elsevier Ltd.
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