Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene

Chisholm, David; Lamb, Rebecca; Pallett, Tommy; Affleck, Valerie; Holden, Claire; Marrison, Joanne; O'Toole, Peter; Ashton, Peter; Newling, Katherine; Steffen, Andreas; Nelson, Amanda; Mahler, Christoph; Valentine, Roy; Blacker, Thomas; Bain, Angus John; Girkin, John M; Marder, Todd B; Whiting, Andrew; Ambler, Carrie A

Abstract

Photoactivation of photosensitisers can be utilised to elicit the production of ROS, for potential therapeutic applications, including the destruction of diseased tissues and tumours. A novel class of photosensitiser, exemplified by DC324, has been designed possessing a modular, low molecular weight ‘drug-like’ structure which is bioavailable and can be photoactivated by UV-A/405 nm or corresponding two-photon absorption of near-IR (800 nm) light, resulting in powerful cytotoxic activity, ostensibly through the production of ROS in a cellular environment. A variety of in vitro cellular assays confirmed ROS formation and in vivo cytotoxic activity was exemplified via irradiation and subsequent targeted destruction of specific areas of a zebrafish embryo.

Citation

Chisholm, D., Lamb, R., Pallett, T., Affleck, V., Holden, C., Marrison, J., O'Toole, P., Ashton, P., Newling, K., Steffen, A., Nelson, A., Mahler, C., Valentine, R., Blacker, T., Bain, A. J., Girkin, J. M., Marder, T. B., Whiting, A., & Ambler, C. A. (2019). Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene. Chemical Science, 10(17), 4673-4683. https://doi.org/10.1039/c9sc00199a

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2019
• Online Publication Date: Mar 21, 2019
• Publication Date: May 7, 2019
• Deposit Date: Mar 21, 2019
• Publicly Available Date: Mar 20, 2020
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Electronic ISSN: 2041-6539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 17
• Pages: 4673-4683
• DOI: https://doi.org/10.1039/c9sc00199a
• Public URL: https://durham-repository.worktribe.com/output/1300383