Targeted delivery of paclitaxel to tumor cells: synthesis and in vitro evaluation
| Autor: | John M. Ndungu, Aiming Sun, Shijun Zhu, Dong M. Shin, Georgia Z. Chen, James P. Snyder, Xu Wang, Chao Yang, Mamoru Shoji, Yang J. Lu |
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| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular endocrine system Umbilical Veins Paclitaxel Tumor cells Antineoplastic Agents Factor VIIa Pharmacology complex mixtures Article Amino Acid Chloromethyl Ketones Tissue factor chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor Drug Discovery Humans IC50 Chemistry Endothelial Cells In vitro Cell culture Drug Resistance Neoplasm Cancer cell Drug delivery Molecular Medicine Endothelium Vascular Drug Screening Assays Antitumor |
| Zdroj: | Journal of medicinal chemistry. 53(8) |
| ISSN: | 1520-4804 |
| Popis: | We previously reported a novel drug delivery system, drug-linker-Phe-Phe-Arg-methylketone-(FFR-mk)-factor VIIa (fVIIa). The method utilizes tissue factor (TF), which is aberrantly and abundantly expressed on many cancer cells. The advantage of this delivery system is its ability to furnish a potent anti-cancer drug specifically to the tumor vasculature and cancer cells. In this paper, we describe the synthesis of paclitaxel (PTX)-Phe-Phe-Arg-chloromethyl ketone (FFR-ck), followed by coupling with fVIIa to form PTX-FFR-mk-fVIIa. FFRck was separately linked to the OH groups at the C2′ or C7 positions of PTX (C2′- or C7-PTX-FFRck), the C2′ analog exhibiting better activity against human head and neck squamous KB 3-1 cells. The activity order against PTX-sensitive KB 3-1 cells is C2′-PTX-FFRmk-fVIIa > PTX >C2′-PTX-FFRck. The C2′-complex shows an IC50 of 12 nM against the PTX-sensitive cell line and 130 nM against PTX-resistant cells. a |
| Databáze: | OpenAIRE |
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