Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, India.
Int J Pharm. 2012 Oct 15;436(1-2):183-93. doi: 10.1016/j.ijpharm.2012.05.078. Epub 2012 Jun 18.
Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.
抗癌药物的疗效受到药物严重不良反应的限制；因此，关键在于设计仅针对癌细胞的靶向递送系统。为此，我们提出了合成聚乙二醇（PEG）-阿霉素（DOX）前药缀合物，其中 N-乙酰葡萄糖胺（NAG）作为靶向部分。所提出的多组分系统的特征在于（1）H NMR、UV 光谱和 HPLC。使用 MCF-7 和 MDA-MB-231 细胞，通过体外细胞动力学和抗癌活性评估多组分系统。分子建模研究表明聚合物缀合物具有空间稳定的构象。有趣的是，与 DOX 药物缀合物相比，具有 NAG 配体的 PEG-DOX 缀合物显示出更高的细胞毒性。此外，与游离 DOX 相比，具有 NAG 和 DOX 的聚合物药物缀合物在癌细胞中表现出增强的内化和保留作用。因此，具有增强的内化和靶向能力的 NAG-DOX 的 PEG 缀合物在靶向抗癌治疗中具有重要意义。
