Hyaluronic acid-paclitaxel conjugate micelles: Synthesis, characterization, and antitumor activity
Hyaluronic acid-paclitaxel conjugate micelles: Synthesis, characterization, and antitumor activity
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DOI：
10.1021/bc8000485
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Park, Tae Gwan
中科院分区：
文献类型：
--
作者：
Lee, Hyukjin;Lee, Kyuri;Park, Tae Gwan
采用一种新的透明质酸增溶方法，在单一有机相中合成了紫杉醇与透明质酸的化学偶联物。通过形成纳米复合物，亲水性HA完全溶解于添加有聚（乙二醇）（PEG）的无水DMSO中。然后在DMSO相中通过酯键将紫杉醇化学缀合至HA，而不修饰极端亲水性的HA。合成并表征了一系列具有不同偶联百分比的HA-紫杉醇偶联物。HA-紫杉醇缀合物在水溶液中自组装以形成纳米尺寸的胶束聚集体，如通过动态光散射（DLS）、原子力显微镜（AFM）和透射电子显微镜（TEM）表征的。在酸性pH条件下从HA-紫杉醇缀合物胶束再生完整形式的紫杉醇。HA-紫杉醇缀合物胶束对HA受体过表达的癌细胞比对HA受体缺陷的细胞表现出更显著的细胞毒性作用，表明它们可以潜在地用作肿瘤特异性纳米颗粒治疗剂。
Chemical conjugates of paclitaxel and hyaluronic acid (HA) were synthesized by utilizing a novel HA solubilization method in a single organic phase. Hydrophilic HA was completely dissolved in anhydrous DMSO with addition of poly(ethylene glycol) (PEG) by forming nanocomplexes. Paclitaxel was then chemically conjugated to HA in the DMSO phase via an ester linkage without modifying extremely hydrophilic HA. A series of HA-paclitaxel conjugates with different conjugation percentages were synthesized and characterized. HA-paclitaxel conjugates self-assembled in aqueous solution to form nanosized micellar aggregates, as characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). An intact form of paclitaxel was regenerated from HA-paclitaxel conjugate micelles at acidic pH conditions. HA-paclitaxel conjugate micelles exhibited more pronounced cytotoxic effect for HA receptor overexpressing cancer cells than for HA receptor deficient cells, suggesting that they can be potentially utilized as tumor-specific nanoparticulate therapeutic agents.