The antiangiogenic efficacy of NGR-modified PEG-DSPE micelles containing paclitaxel (NGR-M-PTX) for the treatment of glioma in rats.

Abstract

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.

• Authors: Bo-Jun Zhao, Xi-Yu Ke, Yue Huang, Xiao-Mei Chen, Xin Zhao, Bing-Xiang Zhao, Wan-liang Lu, Jin-Ning Lou, Xuan Zhang, Qiang Zhang
• Journal: Journal of drug targeting (J Drug Target) Vol. 19 Issue 5 Pg. 382-90 (Jun 2011) ISSN: 1029-2330 [Electronic] England
• PMID: 20677914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Drug Carriers
• Micelles
• NGR peptide
• Oligopeptides
• Phosphatidylethanolamines
• polyethylene glycol-distearoylphosphatidylethanolamine
• Polyethylene Glycols
• Glutamyl Aminopeptidase
• Paclitaxel

Topics

• Angiogenesis Inhibitors (administration & dosage, therapeutic use)
• Animals
• Brain Neoplasms (blood supply, drug therapy, enzymology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid
• Drug Carriers (chemistry)
• Endothelial Cells (drug effects)
• Flow Cytometry
• Glioma (blood supply, drug therapy, enzymology)
• Glutamyl Aminopeptidase (metabolism)
• Male
• Mice
• Micelles
• Microscopy, Fluorescence
• Neoplasm Transplantation
• Oligopeptides (chemistry)
• Paclitaxel (administration & dosage, therapeutic use)
• Particle Size
• Phosphatidylethanolamines (chemistry)
• Polyethylene Glycols (chemistry)
• Rats
• Rats, Sprague-Dawley