Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery.
Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery.
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DOI：
10.1016/j.biomaterials.2009.12.022
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Fabian Suriano;R. Pratt;J. Tan;N. Wiradharma;Alshakim Nelson;Yi-Yan Yang;P. Dubois;J. Hedrick
中科院分区：
文献类型：
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作者：
Fabian Suriano;R. Pratt;J. Tan;N. Wiradharma;Alshakim Nelson;Yi-Yan Yang;P. Dubois;J. Hedrick
含有侧链碳水化合物的聚合物具有多种生物医学应用，特别是在靶向给药方面。本文报道了一类含d-葡萄糖、d-半乳糖和d-甘露糖的两亲性嵌段糖共聚物的合成及其在药物释放中的应用。这些糖共聚物自组装成胶束，在壳层中具有高密度的糖分子，尺寸小于100 nm，即使在载药后尺寸分布也很窄，并且细胞毒性很小，这对药物传递是重要的。以含半乳糖的胶束为例，与ASGP-R阴性的HEK293细胞相比，我们证明了它们对ASGP-R阳性的HepG2肝癌细胞具有很强的靶向性，尽管半乳糖连接在碳酸酯单体的6位。与HEK293相比，HepG2细胞对负载DOX的半乳糖胶束的摄取增强显著增加了DOX的细胞毒性。这种新型的两亲性嵌段糖共聚物作为靶向给药载体具有很大的潜力。
Polymers bearing pendant carbohydrates have a variety of biomedical applications especially in the area of targeted drug delivery. Here we report the synthesis of a family of amphiphilic block glycopolymers containing d glucose, d galactose and d mannose via metal-free organocatalyzed ring-opening polymerization of functional cyclic carbonates generating narrowly dispersed products of controlled molecular weight and end-group fidelity, and their application in drug delivery. These glycopolymers self-assemble into micelles having a high density of sugar molecules in the shell, a size less than 100 nm with narrow size distribution even after drug loading, and little cytotoxicity, which are important for drug delivery. Using galactose-containing micelles as an example, we demonstrate their strong targeting ability towards ASGP-R positive HepG2 liver cancer cells in comparison with ASGP-R negative HEK293 cells although the galactose is attached to the carbonate monomer at 6-position. The enhanced uptake of DOX-loaded galactose-containing micelles by HepG2 cells significantly increases cytotoxicity of DOX as compared to HEK293. This new family of amphiphilic block glycopolymers has great potential as carriers for targeted drug delivery.