Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China.
State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi, District, Dalian 116023, China.
Bioorg Med Chem Lett. 2019 Apr 15;29(8):1019-1022. doi: 10.1016/j.bmcl.2019.02.005. Epub 2019 Feb 6.
Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown significant anti-cancer effects through inhibiting microtubule assembly. However, because of the poor water solubility and obvious side effects, PPT cannot be used in clinical cancer therapy. In order to solve these problems, a novel glutathione-responsive PPT conjugate has been synthesized in which PPT was linked to an anti-mitotic cell penetrating peptide (PRA) via a disulfide linkage. In particular, the as-prepared PPT-PRA conjugate can self-assemble into vesicle in water, furthermore, another anti-cancer drug (doxorubicin was chosen as an example) can be loaded in the vesicle for synergistic drug delivery. For better cancer cells targeting, the vesicle was then modified with folic acid (FA). The results indicated that the as-prepared FA modified drug-loaded vesicle not only could overcome the poor water solubility and side effects of PPT but also exhibited targeted toxicity and synergistic therapeutic effect.
鬼臼毒素（PPT）是一种化疗药物，通过抑制微管组装显示出显著的抗癌效果。然而，由于其水溶性差和明显的副作用，PPT 不能用于临床癌症治疗。为了解决这些问题，我们合成了一种新型的谷胱甘肽响应性 PPT 缀合物，其中 PPT 通过二硫键与抗有丝分裂细胞穿透肽（PRA）连接。特别地，所制备的 PPT-PRA 缀合物可以在水中自组装成囊泡，此外，还可以将另一种抗癌药物（选择多柔比星作为示例）装载在囊泡中进行协同药物递送。为了更好地靶向癌细胞，囊泡用叶酸（FA）进行了修饰。结果表明，所制备的 FA 修饰的载药囊泡不仅可以克服 PPT 的水溶性差和副作用，还表现出靶向毒性和协同治疗效果。
