Alendronate-Conjugated Amphiphilic Hyperbranched Polymer Based on Boltorn H40 and Poly(ethylene glycol) for Bone-Targeted Drug Delivery
Alendronate-Conjugated Amphiphilic Hyperbranched Polymer Based on Boltorn H40 and Poly(ethylene glycol) for Bone-Targeted Drug Delivery
复制标题
基于 Boltorn H40 和聚乙二醇的阿仑膦酸盐共轭两亲性超支化聚合物，用于骨靶向药物输送
DOI：
10.1021/bc3003088
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发表时间：
2012-09-01
影响因子：
4.7
通讯作者：
Zhu, Xinyuan
中科院分区：
文献类型：
--
作者：
Chen, Hongying;Li, Guolin;Zhu, Xinyuan
以疏水性超支化Boltorn H40（H40）核为骨架，引入ALE靶向基团，并引入多个亲水性聚乙二醇（PEG）臂，合成了一种新型的两亲性超支化共聚物，作为骨靶向给药载体。采用核磁共振（NMR）、傅立叶变换红外光谱（FTIR）和凝胶渗透色谱（GPC）对H40-star-PEG/ALE的星星共聚物进行了表征。透射电子显微镜（TEM）和动态光散射（DLS）结果表明，H40-star-PEG/ALE具有高度支化的结构，在水溶液中可形成胶束。采用MTT法和红细胞溶解法分别测定H40-star-PEG/ALE胶束对NIH/3 T3正常细胞的细胞毒性和溶血作用。以阿霉素（DOX）为模型抗癌药物，将其包埋于H40-star-PEG/ALE胶束中。MTT法检测载阿霉素胶束对人头颈癌细胞系HN-6的抗肿瘤活性。羟基磷灰石（HA）结合试验证实了H40-star-PEG/ALE胶束对骨的强亲和力。这些结果表明，H40-star-PEG/ALE胶束是非常有前途的骨靶向药物载体的骨转移。
A novel type of alendronate(ALE)-conjugated amphiphilic hyperbranched copolymer based on a hydrophobic hyperbranched Boltorn H40 (H40) core with ALE targeting moiety and many hydrophilic poly(ethylene glycol) (PEG) arms was synthesized as a carrier for bone-targeted drug delivery. The star copolymer H40-star-PEG/ALE was characterized using nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FTIR), and gel permeation chromatography (GPC) analysis. Benefiting from its highly branched structure, H40-star-PEG/ALE could form micelles in aqueous solution, which was confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The cytotoxicity and hemolysis of the H40-star-PEG/ALE micelles were evaluated via methylthiazoletetrazolium (MTT) assay against NIH/3T3 normal cells and red blood cell (RBC) lysis assay, respectively. As a model anticancer drug, doxorubicin (DOX) was encapsulated into the H40-star-PEG/ALE micelles. The anticancer activity of DOX-loaded micelles was evaluated by MTT assay against an HN-6 human head and neck carcinoma cell line. The strong affinity of H40-star-PEG/ALE micelles to bone was confirmed by the hydroxyapatite (HA) binding assay. These results indicate that the H40-star-PEG/ALE micelles are highly promising bone-targeted drug carriers for skeletal metastases.