Li Xia, McTaggart Matt, Malardier-Jugroot Cecile
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON, Canada.
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON, Canada.
Biophys Chem. 2016 Jul-Aug;214-215:17-26. doi: 10.1016/j.bpc.2016.04.002. Epub 2016 Apr 27.
We report the computational analysis, synthesis and characterization of folate functionalized poly(styrene-alt-maleic anhydride), PSMA for drug delivery purpose. The selection of the proper linker between the polymer and the folic acid group was performed before conducting the synthesis using Density Functional Theory (DFT). The computational results showed the bio-degradable linker 2, 4-diaminobutyric acid, DABA as a good candidate allowing flexibility of the folic acid group while maintaining the pH sensitivity of PSMA, used as a trigger for drug release. The synthesis was subsequently carried out in multi-step experimental procedures. The functionalized polymer was characterized using InfraRed spectroscopy, Nuclear Magnetic Resonance and Dynamic Light Scattering confirming both the chemical structure and the pH responsiveness of PSMA-DABA-Folate polymers. This study provides an excellent example of how computational chemistry can be used in selection process for the functional materials and product characterization. The pH sensitive polymers are expected to be used in delivering anti-cancer drugs to solid tumors with overly expressed folic acid receptors.
我们报告了用于药物递送目的的叶酸功能化聚（苯乙烯 - 马来酸酐）（PSMA）的计算分析、合成及表征。在使用密度泛函理论（DFT）进行合成之前，对聚合物与叶酸基团之间合适的连接体进行了选择。计算结果表明，可生物降解的连接体2,4 - 二氨基丁酸（DABA）是一个很好的候选者，它能使叶酸基团具有灵活性，同时保持PSMA的pH敏感性，用作药物释放的触发因素。随后通过多步实验程序进行了合成。使用红外光谱、核磁共振和动态光散射对功能化聚合物进行了表征，证实了PSMA - DABA - 叶酸聚合物的化学结构和pH响应性。这项研究提供了一个很好的例子，说明了计算化学如何用于功能材料的选择过程和产品表征。预计pH敏感聚合物将用于向叶酸受体过度表达的实体瘤递送抗癌药物。
