NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, Florida 32816, USA.
J Am Chem Soc. 2011 Oct 19;133(41):16680-8. doi: 10.1021/ja207463b. Epub 2011 Sep 27.
Herein we describe the design and synthesis of a folate-doxorubicin conjugate with activatable fluorescence and activatable cytotoxicity. In this study we discovered that the cytotoxicity and fluorescence of doxorubicin are quenched (OFF) when covalently linked with folic acid. Most importantly, when the conjugate is designed with a disulfide bond linking the targeting folate unit and the cytotoxic doxorubicin, a targeted activatable prodrug is obtained that becomes activated (ON) within the cell by glutathione-mediated dissociation and nuclear translocation, showing enhanced fluorescence and cellular toxicity. In our novel design, folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin's fluorescence.
在此，我们描述了一种叶酸-阿霉素缀合物的设计和合成，该缀合物具有可激活的荧光和细胞毒性。在这项研究中，我们发现阿霉素的细胞毒性和荧光在与叶酸共价连接时被猝灭（OFF）。最重要的是，当缀合物设计为通过二硫键连接靶向叶酸单元和细胞毒性阿霉素时，可获得一种靶向激活前药，该前药在细胞内通过谷胱甘肽介导的解离和核转位而被激活（ON），表现出增强的荧光和细胞毒性。在我们的新设计中，叶酸既充当叶酸受体的靶向配体，也充当阿霉素荧光的猝灭剂。
