Dcona M Michael, Sheldon Jonathon E, Mitra Deboleena, Hartman Matthew C T
The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Internal Medicine, Virginia Commonwealth University, 1101 E. Marshall St., Richmond, VA 23298, USA.
The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Chemistry, Virginia Commonwealth University, 1001 West Main St., Richmond, VA 23284, USA.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):466-469. doi: 10.1016/j.bmcl.2016.12.036. Epub 2016 Dec 18.
A major area of cancer research focuses on improving the specificity of therapeutic agents by engineering drug-delivery vehicles that target overexpressed receptors on tumor cells. One of the most commonly used approaches involves targeting of folate receptors using folic acid conjugated to a drug-containing macromolecular cargo. Once internalized via endocytosis, the drugs must be released from these constructs in order to avoid being trapped in the endosomes. Here, we describe the synthesis of a small-molecule conjugate that couples folic acid to doxorubicin via a photocleavable linker. Using HPLC we show that the doxorubicin can be released with light rapidly and with high efficiency. This approach has advantages over macromolecular systems due to its simplicity and efficiency.
癌症研究的一个主要领域致力于通过构建靶向肿瘤细胞上过表达受体的药物递送载体来提高治疗药物的特异性。最常用的方法之一是利用与含药大分子载体偶联的叶酸来靶向叶酸受体。一旦通过内吞作用内化，药物必须从这些构建体中释放出来，以避免被困在内体中。在此，我们描述了一种小分子偶联物的合成，该偶联物通过光可裂解连接子将叶酸与阿霉素偶联。使用高效液相色谱法，我们表明阿霉素可以被光快速且高效地释放。由于其简单性和高效性，这种方法相对于大分子系统具有优势。
