Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Carbohydr Polym. 2017 Apr 1;161:33-41. doi: 10.1016/j.carbpol.2016.12.070. Epub 2016 Dec 31.
The acid-sensitive polymer prodrugs have attracted increasing attention because of their selective intratumoral or intracellular drug release. Herein, two intracellular acid-sensitive dextran-doxorubicin (Dex-DOX) conjugates with similar drug binding rate were synthesized through the Schiff base reaction between the aldehyde group in the oxidized Dex with different lengths and the amino group of DOX. The amphiphilic Dex-DOX conjugates self-assembled into micellar nanoparticles in phosphate-buffered saline (PBS). The micelle of prodrug with longer Dex, that is, Dex-DOX, exhibited smaller size, quicker drug release, higher cell internalization, and stronger tumor suppression with upregulated security in comparison with the one with shorter Dex, that is, Dex-DOX. Therefore, the molecular weight of prodrug backbone could adjust the properties, and a higher molecular weight endowed the Dex-DOX conjugate with a better antitumor efficacy in a limited number of tested samples.
由于其具有选择性的肿瘤内或细胞内药物释放，酸敏感聚合物前药受到了越来越多的关注。本文通过醛基与 DOX 氨基之间的席夫碱反应，合成了两种结合率相似的细胞内酸敏感葡聚糖-阿霉素（Dex-DOX）缀合物。两亲性 Dex-DOX 缀合物在磷酸盐缓冲盐水（PBS）中自组装成胶束纳米粒。与较短葡聚糖的 Dex-DOX 相比，前药的葡聚糖更长，即 Dex-DOX，表现出更小的粒径、更快的药物释放、更高的细胞内化和更强的肿瘤抑制作用，同时提高了安全性。因此，前药主链的分子量可以调节性能，在有限数量的测试样本中，较高的分子量赋予 Dex-DOX 缀合物更好的抗肿瘤疗效。
