Targeted Delivery of Anticancer Agents via a Dual Function Nanocarrier with an Interfacial Drug-Interactive Motif

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• 作者：Xiaolan Zhang ; Yixian Huang ; Wenchen Zhao ; Hao Liu ; Rebecca Marquez ; Jianqin Lu ; Peng Zhang ; Yifei Zhang ; Jiang Li ; Xiang Gao ; Raman Venkataramanan ; Liang Xu ; Song Li
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：November 10, 2014
• 年：2014
• 卷：15
• 期：11
• 页码：4326-4335
• 全文大小：728K
• ISSN：1526-4602

文摘

We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG_5k鈥揊TS₂ led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG_5k鈥揊moc鈥揊TS₂ showed sustained release kinetics slower than those of DOX loaded in PEG_5k鈥揊TS₂. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG_5k鈥揊moc鈥揊TS₂ was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG_5k鈥揊moc鈥揊TS₂ mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG_5k鈥揊moc鈥揊TS₂ led to superior antitumor activity over other treatments including drugs formulated in PEG_5k鈥揊TS₂ in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.