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论文类型：期刊论文

发表时间：2019-04-15

发表刊物：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录刊物：PubMed、SCIE

卷号：29

期号：8

页面范围：1019-1022

ISSN号：0960-894X

关键字：Podophyllotoxin; Stimuli-responsive; Drug delivery; Cancer therapy; Cell penetrating peptide

摘要：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.