Sulfation patterns determine cellular internalization of heparin-like polysaccharides.
Sulfation patterns determine cellular internalization of heparin-like polysaccharides.
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DOI：
10.1021/mp300679a
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发表时间：
2013-04-01
影响因子：
4.9
通讯作者：
Kuberan B
中科院分区：
文献类型：
--
作者：
Raman K;Mencio C;Desai UR;Kuberan B
肝素是一种高度硫酸化的多糖，具有生物学相关的抗凝剂和抗癌剂作用。虽然众所周知，改变肝素的硫酸化模式可以极大地影响其结合生长因子和其他细胞外分子的能力，但人们对肝素的细胞摄取以及硫酸化模式在影响其内化中的作用知之甚少。在这项研究中，我们化学合成了几种由多种硫酸化模式组成的荧光标记肝素。使用阴离子交换色谱和尺寸排阻色谱对这些多糖进行了彻底的表征。随后，我们利用流式细胞术和共聚焦成像表明硫酸化模式对多种细胞类型的肝素摄取量有不同的影响。这项研究首次全面分析了硫酸化模式对肝素或硫酸类肝素多糖细胞内化的影响。这项研究的结果扩展了当前有关肝素内化的知识，并为开发更有效的基于肝素的药物缀合物用于细胞内药物输送应用提供了见解。
Heparin is a highly sulfated polysaccharide which serves biologically relevant roles as an anticoagulant and anti-cancer agent. While it is well known that modification of heparin’s sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently-labeled heparins consisting of a variety of sulfation patterns. These polysaccharides were thoroughly characterized using anion exchange chromatography and size exclusion chromatography. Subsequently, we utilized flow cytometry and confocal imaging to show that sulfation patterns differentially affect the amount of heparin uptake in multiple cell types. This study provides the first comprehensive analysis of the effect of sulfation pattern on the cellular internalization of heparin or heparan sulfate like polysaccharides. The results of this study expand current knowledge regarding heparin internalization and provide insights into developing more effective heparin-based drug conjugates for applications in intracellular drug delivery.
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