期刊
ANTI-CANCER DRUGS
卷 22, 期 5, 页码 409-415出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e328342050d
关键词
angiogenesis; antiangiogenesis; endostatin; endothelial cell; integrin; RGD ligands; tumor targeting
资金
- Major New Drug Creation Science and Technology Special Project of China [2009ZX09103-659]
Many antitumor drugs have a limited ability to penetrate more than a few cell diameters from blood vessels into solid tumors, which limits their effectiveness. In this study, we investigated whether the biological activity of endostatin can be enhanced by the addition of an integrin-targeting and permeability-enhancing sequence. The internalization RGD (CRGDKGPDC; iRGD) sequence was added at the carboxyl terminus of endostatin. Modification of endostatin with the iRGD motif showed specific and increased binding to endothelial cells; the increased binding correlated with an improved antiangiogenic property. iRGD-modified endostatin was more effective than human endostatin in inhibiting liver cancer growth in athymic mice. The finding indicates that addition of a vascular targeting and permeability sequence can enhance the biological activity of an antiangiogenic molecule and tumor targeting. Anti-Cancer Drugs 22:409-415 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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