期刊
BIOMATERIALS
卷 34, 期 38, 页码 10160-10171出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.09.043
关键词
Biodegradable polymers; Cancer nanotechnology; Drug targeting; Molecular biomaterials; Pharmaceutical nanotechnology; Nanomedicine
资金
- Singapore China Cooperative Research Project
- Agency of Science, Technology and Research (A*STAR), Singapore
- Chinese Ministry of Science and Technology (MOST) [R-398-000-077-305]
- NUS FSF [R-397-000-136-731]
- FRC [R-397-000-136-112]
We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for targeted delivery of docetaxel as a model anticancer drug for treatment of the triple negative breast cancer (TNBC), which shows no expression of either one of the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) and is thus more difficult to be treated than the positive breast cancer. Such micelles are of desired particle size, drug loading, drug encapsulation efficiency and drug release profile. Their surface morphology, surface charge and surface chemistry were also characterized. The fibroblast cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of docetaxel formulated in the micelles. The high IC50 value, which is the drug concentration needed to kill 50% of the cells in a designated period such as 24 h, obtained from Taxotere (R) showed that the TNBC cells are indeed more resistant to the free drug than the positive breast cancer cells. However, the therapeutic effects of docetaxel could be greatly enhanced by the formulation of Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold higher efficiency than Taxotere (R) for the MDA MB 468 and MDA MB 231 cell lines respectively. (C) 2013 Elsevier Ltd. All rights reserved.
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