基于THz-CARS显微镜的DNA低频振动谱及其与顺铂插层绑定机理研究

顺铂可通过与DNA插层绑定杀死癌细胞，在癌症化疗中有广泛的应用前景。本项目针对顺铂抗癌药物与DNA插层绑定机理这一科学问题，在广义能量片段模型基础上构建溶液环境下DNA片段新模型，采用密度泛函理论（DFT）方法计算DNA低频振动模式，分析DNA低频振动与其内部结构之间的关系，揭示DNA低频振动所具有的生物功能，结合太赫兹波段相干反斯托克斯拉曼散射（THz-CARS）显微镜与低频波段自发拉曼散射技术实验观测DNA溶液的低频振动模式，验证理论模拟结果，以DAPI（二脒基苯基吲哚）与DNA溶液发生的Groove绑定过程为参考实验，最后通过分析对比DNA发生插层绑定与发生Groove绑定前后其低频振动模式变化的区别与内在联系，探究DNA低频振动模式在插层绑定过程中的作用，建立低频振动与DNA插层绑定之间的关系。项目研究结果将为抗癌药物与DNA插层绑定机理研究提供一种新思路和科学依据。

Cisplatin can kill cancer cells by intercalation binding into DNA molecules, and find wide applications in chemotherapeutic therapy of cancers. This research is aimed at elucidating the mechanism of intercalation binding of an anti-cancer drug (cisplatin) into DNA molecule. We will build a new model of DNA fragment in a solution environment based on the generalized energy-based fragmentation. By using density functional theory (DFT) method, we will calculate the low-frequency vibrational modes of the DNA fragments. Based on the calculation we will analyze the relation between the internal structure and the low-frequency vibrations. We will also reveal the corresponding biological functions of the low-frequency vibrations. Combining the terahertz coherent anti-stokes Raman scattering (THz-CARS) microscope and the low-frequency spontaneous Raman scattering technique, we will experimentally observe the low-frequency vibrational modes of DNA solution and verify the theoretical simulations. Using the experiment of Groove binding between DNA and DAPI as a reference, we will explore the role of the low-frequency vibrations of DNA in the intercalation binding between the cisplatin and DNA by analyzing and comparing the distinctions and linkages of the low-frequency vibrational modes changes of the DNA molecules after the intercalation binding and Groove binding. Finally, we will establish a relationship between the low-frequency vibrations of DNA and the mechanism of the intercalation binding. The research results will provide a new idea and a scientific basis for the research on the mechanism of intercalation binding between the anti-cancer drug and DNA molecule.