The antiangiogenic efficacy of NGR-modified PEG–DSPE micelles containing paclitaxel (NGR-M-PTX) for the treatment of glioma in rats
| Autor: | Jinning Lou, Xiyu Ke, Xin Zhao, Qiang Zhang, Bing-Xiang Zhao, Xiao-Mei Chen, Yue Huang, Xuan Zhang, Bo-Jun Zhao, Wan-Liang Lu |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Programmed cell death Paclitaxel Cell Survival Pharmaceutical Science Angiogenesis Inhibitors Pharmacology Glutamyl Aminopeptidase Polyethylene Glycols Flow cytometry Rats Sprague-Dawley Mice chemistry.chemical_compound In vivo Cell Line Tumor Glioma medicine Animals Particle Size Cytotoxicity Chromatography High Pressure Liquid Micelles Cell Proliferation Drug Carriers medicine.diagnostic_test Brain Neoplasms business.industry Phosphatidylethanolamines Endothelial Cells Flow Cytometry medicine.disease In vitro Rats Microscopy Fluorescence chemistry Cell culture business Oligopeptides Neoplasm Transplantation |
| Zdroj: | Journal of Drug Targeting. 19:382-390 |
| ISSN: | 1029-2330 1061-186X |
| Popis: | Aminopeptidase N (APN), recognized by Asn-Gly-Arg (NGR) peptides, is expressed in the pericytes associated with the BBB, and the main objective of this study is to confirm the hypothesis that NGR-modified DSPE-PEG micelles containing paclitaxel (NGR-M-PTX) can bind to and kill brain tumor angiogenic blood vessels and penetrate into the brain tumor interstitial space, resulting in direct cell death. NGR-M-PTX is prepared by a thin-film hydration method. The in vitro targeting characteristics of NGR-modified micelles on BMEC (murine brain microvascular endothelial cells) were investigated. The effect of NGR-M-PTX on BMEC proliferation and the cytotoxicity of NGR-M-PTX in C6 glioma cells were also tested. The antitumor activity NGR-M-PTX was evaluated in C6 glioma tumor-bearing rats in vivo. The particle size of NGR-M-PTX was approximately 54.2 nm. The drug encapsulation efficiency of NGR-M-PTX was 82.11 ± 2.82%. The cellular coumarin-6 level of NGR-M-coumarin-6 in the BMEC was about 2.2-fold higher than that of M-coumarin-6. BMEC proliferation was significantly inhibited by NGR-M-PTX. NGR-M-PTX had a much lower IC(50) value than M-PTX and free drug. The growth of C6 glioma tumor was markedly inhibited by NGR-M-PTX compared with Taxol. In conclusion, our results show that antiangiogenic therapy using NGR-M-PTX exhibits potent in vivo antitumor activity in a C6 glioma-bearing animal model. |
| Databáze: | OpenAIRE |
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