Combination of Small Molecule Prodrug and Nanodrug Delivery: Amphiphilic Drug鈥揇rug Conjugate for Cancer Therapy

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• 作者：Ping Huang ; Dali Wang ; Yue Su ; Wei Huang ; Yongfeng Zhou ; Daxiang Cui ; Xinyuan Zhu ; Deyue Yan
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：August 20, 2014
• 年：2014
• 卷：136
• 期：33
• 页码：11748-11756
• 全文大小：704K
• ISSN：1520-5126

文摘

All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug鈥揹rug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir鈥揅b conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir鈥揅b ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.