Department of Chemical Physics, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
Friedrich Schiller University Jena, Institute of Physical Chemistry and Abbe Center of Photonics, Helmholtzweg 4, Jena 07743, Germany.
Anal Chem. 2024 Jun 4;96(22):8905-8913. doi: 10.1021/acs.analchem.3c05372. Epub 2024 May 21.
Chemotherapeutic anthracyclines, like doxorubicin (DOX), are drugs endowed with cytostatic activity and are widely used in antitumor therapy. Their molecular mechanism of action involves the formation of a stable anthracycline-DNA complex, which prevents cell division and results in cell death. It is known that elevated DOX concentrations induce DNA chain loops and overlaps. Here, for the first time, tip-enhanced Raman scattering was used to identify and localize intercalated DOX in isolated double-stranded calf thymus DNA, and the correlated near-field spectroscopic and morphologic experiments locate the DOX molecules in the DNA and provide further information regarding specific DOX-nucleobase interactions. Thus, the study provides a tool specifically for identifying intercalation markers and generally analyzing drug-DNA interactions. The structure of such complexes down to the molecular level provides mechanistic information about cytotoxicity and the development of potential anticancer drugs.
化疗蒽环类药物，如多柔比星（DOX），是具有细胞抑制活性的药物，广泛用于抗肿瘤治疗。它们的作用机制是形成稳定的蒽环类-DNA 复合物，阻止细胞分裂并导致细胞死亡。已知升高的 DOX 浓度会诱导 DNA 链环和重叠。在这里，首次使用尖端增强拉曼散射来识别和定位分离的双链小牛胸腺 DNA 中的嵌入 DOX，相关的近场光谱和形态学实验将 DOX 分子定位在 DNA 中，并提供有关特定 DOX-核苷碱基相互作用的进一步信息。因此，该研究提供了一种专门用于识别嵌入标记并一般分析药物-DNA 相互作用的工具。此类复合物的结构一直到分子水平，为细胞毒性和潜在抗癌药物的开发提供了关于机制的信息。
