Application of Stimulated Raman Scattering (SRS) microscopy for evaluation of olaparib biodistribution in an ovarian cancer cell line

Craig F. Steven; Manasa Punaha-Ravindra; Martin Lee; William Brownlee; Paul Davey; Elisabetta Chiarparin; Valerie G. Brunton; Alison N. Hulme

doi:10.1117/12.2647240

14 March 2023 Application of Stimulated Raman Scattering (SRS) microscopy for evaluation of olaparib biodistribution in an ovarian cancer cell line

Craig F. Steven, Manasa Punaha-Ravindra, Martin Lee, William Brownlee, Paul Davey, Elisabetta Chiarparin, Valerie G. Brunton, Alison N. Hulme

Author Affiliations +

Proceedings Volume 12357, Visualizing and Quantifying Drug Distribution in Tissue VII; 123570G (2023) https://doi.org/10.1117/12.2647240
Event: SPIE BiOS, 2023, San Francisco, California, United States

Abstract

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.

Conference Presentation

Citation Download Citation

Craig F. Steven, Manasa Punaha-Ravindra, Martin Lee, William Brownlee, Paul Davey, Elisabetta Chiarparin, Valerie G. Brunton, and Alison N. Hulme "Application of Stimulated Raman Scattering (SRS) microscopy for evaluation of olaparib biodistribution in an ovarian cancer cell line", Proc. SPIE 12357, Visualizing and Quantifying Drug Distribution in Tissue VII, 123570G (14 March 2023); https://doi.org/10.1117/12.2647240

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