Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth
Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth
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DOI：
10.1021/bc800173m
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发表时间：
2008-07-01
影响因子：
4.7
通讯作者：
Lee, Yong-Kyu
中科院分区：
文献类型：
--
作者：
Cho, Kwang Jae;Moon, Hyun Tae;Lee, Yong-Kyu
我们描述了新的DOC（脱氧胆酸钠）-肝素纳米粒子在体内肿瘤靶向和抑制血管生成的基础上化学共轭和增强的渗透性和保留（EPR）的效果。肝素作为一种有效的抗凝剂已有70年的历史，最近发现它能抑制刺激肿瘤周围平滑肌细胞的生长因子的活性。从结果来看，DOC和肝素通过肝素的羧基与胺化脱氧胆酸钠的胺基结合而缀合。在动物研究中，DOC-肝素VI（8.5 mol DOC与1.0 mol肝素偶联）的抗肿瘤作用大于单独肝素。我们证实，结合肝素保留其抑制与血管生成因子结合的能力，显示出内皮小管形成的显著减少。这些结果提供了新的见解无毒抗癌药物载体以及设计的多功能生物共轭物靶向药物输送。
We describe new DOC (sodium deoxycholate)-heparin nanoparticles for in vivo tumor targeting and inhibition of angiogenesis based on chemical conjugation and the enhanced permeability and retention (EPR) effect. Heparin has been used as a potent anticoagulant agent for 70 years, and has recently been found to inhibit the activity of growth factors which stimulate the smooth muscle cells around tumor. From the results, DOC and heparin were conjugated by bonding carboxyl groups of heparin with amine groups of aminated sodium deoxycholate. Larger antitumor effects of the DOC-heparin VI (8.5 mol of DOC coupled with 1.0 mol heparin) were achieved in animal studies, compared to heparin alone. We confirmed that the conjugated heparin retained its ability to inhibit binding with angiogenic factor, showing a significant decrease in endothelial tubular formation. These results provide new insights into the nontoxic anticancer drug carrier as well as the design of multifunctional bioconjugates for targeted drug delivery.