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., …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