Journal
BIOMATERIALS
Volume 34, Issue 13, Pages 3411-3421Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.01.009
Keywords
Biodegradable polymers; Cancer nanotechnology; Molecular biomaterials; Nanomedicine; Anticancer drugs; SiRNA
Funding
- Agency of Science, Technology and Research (A*STAR), Singapore [R-398-000-077-305]
- Chinese Ministry of Science and Technology (MOST) [R-398-000-077-305]
- NUS FSF grant [R-397-000-136-731]
- NUS FRC grant [R-397-000-136-112]
- National University of Singapore
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We developed a drug delivery system of herceptin-conjugated micelles, which consist of vitamin E TPGS and TPGS-siRNA conjugates, for targeted co-delivery of docetaxel and polo-like kinase 1 siRNA to achieve synergistic effects between the anticancer drug and the small interfering RNA responsible for multidrug resistance. The TPGS-siRNA conjugate is made through disulfide bond that could enable a pH-sensitive intracellular release. The load ratio between siPlk1 and docetaxel could be controlled by adjusting the siPlk1-TPGS to TPGS ratio as well as the drug to polymer ratio. NIH3T3, MCF7, and SK-BR-3 cell lines, which are of low, moderate and high HER2 overexpression, were employed to obtain proof-of-concept experimental results for the advantages of such a design. It has been shown that the IC50, which is the drug concentration needed to kill 50% of the cancer cells in a designated time period, was 1.72, 0.042, 0.0032 and 0.000671 mu g/mL for SK-BR-3 cells after 24 h treatment by Taxotere (R), and docetaxel formulated in the TPGS micelles, the TPGS-siPlk1/TPGS micelles and the herceptin-conjugated TPGS-siPlk1/TPGS micelles, respectively. (C) 2013 Elsevier Ltd. All rights reserved.
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