Self-Assembled Nanoparticles of Amphiphilic Twin Drug from Floxuridine and Bendamustine for Cancer Therapy

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• 作者：Ting Zhang ; Ping Huang ; Leilei Shi ; Yue Su ; Linzhu Zhou ; Xinyuan Zhu ; Deyue Yan
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：July 6, 2015
• 年：2015
• 卷：12
• 期：7
• 页码：2328-2336
• 全文大小：430K
• ISSN：1543-8392

文摘

We report here an amphiphilic twin drug strategy directly using small molecular hydrophilic and hydrophobic anticancer drugs to self-assemble into nanoparticles with a high and fixed drug content, which can solve problems of anticancer drug delivery including poor water solubility, low therapeutic indices, and severe side effects. The twin drug has been prepared by the esterification of the hydrophilic anticancer drug floxuridine (FdU) with the hydrophobic anticancer drug bendamustine (BdM). Due to its inherent amphiphilicity, the FdU鈥揃dM twin drug can self-assemble into stable and well-defined nanoparticles. After FdU鈥揃dM twin drug enters into cells, the ester linkage between hydrophilic and hydrophobic drugs is readily cleaved by hydrolysis to release free FdU and BdM. Since both FdU and BdM can kill cancer cells, the FdU鈥揃dM twin drug nanoparticles can overcome the multidrug resistance (MDR) of tumor cells and present an excellent anticancer activity. This strategy can be extended to other hydrophilic and hydrophobic anticancer drugs to synthesize amphiphilic twin drugs which can form nanoparticles to self-deliver drugs for cancer therapy.