Disulfide Bond Bridge Insertion Turns Hydrophobic Anticancer Prodrugs into Self-Assembled Nanomedicines

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• 作者：Yongjun Wang ; Dan Liu ; Qingchuan Zheng ; Qiang Zhao ; Hongjuan Zhang ; Yan Ma ; John K. Fallon ; Qiang Fu ; Matthew T. Haynes ; Guimei Lin ; Rong Zhang ; Dun Wang ; Xinggang Yang ; Linxiang Zhao ; Zhonggui He ; Feng Liu
• 刊名：Nano Letters
• 出版年：2014
• 出版时间：October 8, 2014
• 年：2014
• 卷：14
• 期：10
• 页码：5577-5583
• 全文大小：524K
• ISSN：1530-6992

文摘

It is commonly observed that hydrophobic molecules alone cannot self-assemble into stable nanoparticles, requiring amphiphilic or ionic materials to support nanoparticle stability and function in vivo. We report herein newly self-assembled nanomedicines through entirely different mechanisms. We present proof-of-concept methodology and results in support of our hypothesis that disulfide-induced nanomedicines (DSINMs) are promoted and stabilized by the insertion of a single disulfide bond into hydrophobic molecules, in order to balance the competition between intermolecular forces involved in the self-assembly of nanomedicines. This hypothesis has been explored through diverse synthetic compounds, which include four first-line chemotherapy drugs (paclitaxel, doxorubicin, fluorouracil, and gemcitabine), two small-molecule natural products and their derivatives, as well as a fluorescent probe. Such an unprecedented and highly reproducible system has the potential to serve as a synthetic platform for a wide array of safe and effective therapeutic and diagnostic nanomedicine strategies.

Keywords:

nanomaterials; nanomedicines; nanoparticles; self-assemble; prodrug; disulfide bond