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  • Title: Targeted co-delivery of docetaxel and siPlk1 by herceptin-conjugated vitamin E TPGS based immunomicelles.
    Author: Zhao J, Mi Y, Feng SS.
    Journal: Biomaterials; 2013 Apr; 34(13):3411-21. PubMed ID: 23375951.
    Abstract:
    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 IC(50), 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 μg/mL for SK-BR-3 cells after 24 h treatment by Taxotere(®), and docetaxel formulated in the TPGS micelles, the TPGS-siPlk1/TPGS micelles and the herceptin-conjugated TPGS-siPlk1/TPGS micelles, respectively.
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