title: Targeted co-delivery of docetaxel and siPlk1 by herceptin-conjugated vitamin E TPGS based immunomicelles.
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.
authors: Department of Bioengineering, Faculty of Engineering, National University of Singapore, Block EA, #03-12, 9 Engineering Drive 1, Singapore 117576, Singapore.
authors: Jing
authors: J
authors: Zhao
authors: Yu
authors: Y
authors: Mi
authors: Si-Shen
authors: SS
authors: Feng
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D000077143:Docetaxel; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011092:Polyethylene Glycols / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D012542:Scattering, Radiation; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D059008:Time-Lapse Imaging; D014162:Transfection; D000068878:Trastuzumab; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D000097869:Polo-Like Kinase 1
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018797:Cell Cycle Proteins; D000077143:Docetaxel; D008823:Micelles; D011092:Polyethylene Glycols; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D043823:Taxoids; D000068878:Trastuzumab; D014810:Vitamin E; D000097869:Polo-Like Kinase 1; C014225:tocophersolan