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

[Image: see text] 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)–FTS(2) led to further improvement in both drug loading capacity and formulation stab...

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Detalles Bibliográficos
Autores principales: Zhang, Xiaolan, Huang, Yixian, Zhao, Wenchen, Liu, Hao, Marquez, Rebecca, Lu, Jianqin, Zhang, Peng, Zhang, Yifei, Li, Jiang, Gao, Xiang, Venkataramanan, Raman, Xu, Liang, Li, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229023/
https://www.ncbi.nlm.nih.gov/pubmed/25325795
http://dx.doi.org/10.1021/bm501339j
Descripción
Sumario:[Image: see text] 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)–FTS(2) led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG(5k)–Fmoc–FTS(2) showed sustained release kinetics slower than those of DOX loaded in PEG(5k)–FTS(2). The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG(5k)–Fmoc–FTS(2) was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG(5k)–Fmoc–FTS(2) 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)–Fmoc–FTS(2) led to superior antitumor activity over other treatments including drugs formulated in PEG(5k)–FTS(2) 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.