Application of Stimulated Raman Scattering (SRS) microscopy for evaluation of olaparib biodistribution in an ovarian cancer cell line
Application of Stimulated Raman Scattering (SRS) microscopy for evaluation of olaparib biodistribution in an ovarian cancer cell line
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应用受激拉曼散射 (SRS) 显微镜评估奥拉帕尼在卵巢癌细胞系中的生物分布
DOI：
10.1117/12.2647240
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Steven C
中科院分区：
文献类型：
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作者：
Steven C
近年来，受激拉曼散射显微镜（SRS）已成为药物成像的重要工具。通过调整药物天然结构中化学键的振动频率，通常可以实现无标签成像，从而可以研究药物的药代动力学、代谢和生物分布。然而，由于大约95%的fda批准的药物缺乏合适的拉曼活性片段，因此开发小而高拉曼活性的标签对于充分利用该技术进行药物成像至关重要。此外，目前可用的拉曼标签，如众所周知的双芳基丁二炔（BADY）标签和其他聚乙烯标签，并没有优化用于跟踪小生物分子，主要是由于溶解性差和费力、昂贵的合成。我们考虑了候选标签的物理化学性质来设计和合成改进的BADY类似物。新的body标签附着在PARP抑制剂olaparib上，首次通过拉曼光谱揭示了PARP的生物分布信息。化合物亚细胞定位的差异与实验确定的药物相似性预测因子（如极性表面积（PSA）和log d）相关。使用SRS和基于荧光的技术进行了确定药物靶标结合程度的研究，这将为未来的标签设计提供信息，并提供药物在细胞中的作用的重要信息。
In recent years, stimulated Raman Scattering (SRS) microscopy has emerged as an important tool for drug imaging. By tuning to the vibrational frequency of chemical bonds within a drug’s native structure, label-free imaging can often be achieved, allowing investigation of drug pharmacokinetics, metabolism and biodistribution. However, with ca. 95% of FDA-approved drugs lacking a suitable Raman-active moiety, the development of small, highly Raman-active tags is essential to take full advantage of the technique in drug imaging. Moreover, currently available Raman tags, such as the widely known bisaryl butadiyne (BADY) tag and other polyyne tags, are not optimised for tracking small biomolecules, primarily due to poor solubility and laborious, expensive syntheses. We have considered the physicochemical properties of tag candidates to design and synthesise improved BADY analogues. The new BADY tags were attached to the PARP inhibitor olaparib, revealing information on biodistribution by Raman spectroscopy for the first time. Differences in the subcellular localisation of the compounds were correlated with experimentally determined predictors of drug-likeness such as polar surface area (PSA) and log D. Studies to determine the extent of drug-target engagement were carried out using both SRS and fluorescence-based techniques, which will inform future tag design and provide vital information on drug action in cells.
DOI：
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发表时间：
2007
期刊：
影响因子：
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作者：
R. Mannhold
通讯作者：
R. Mannhold