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dc.contributor.authorRaza, Ahtasham
dc.contributor.authorArcher, Stuart A
dc.contributor.authorFairbanks, Simon D
dc.contributor.authorSmitten, Kirsty L.
dc.contributor.authorBotchway, Stanley W.
dc.contributor.authorThomas, Jim A
dc.contributor.authorMacNeil, Sheila
dc.contributor.authorHaycock, John W.
dc.date.accessioned2020-02-25T16:02:41Z
dc.date.available2020-02-25T16:02:41Z
dc.date.issued2020-02-17
dc.identifier.citationRaza, A., Archer, S.A., Fairbanks, S.D., Smitten, K.L., Botchway, S.W., Thomas, J.A., MacNeil, S. and Haycock, J.W., (2020). 'A dinuclear ruthenium (II) complex excited by near-infrared light through two-photon absorption induces phototoxicity deep within hypoxic regions of melanoma cancer spheroids'. Journal of the American Chemical Society, pp. 1-16. DOI: 10.1021/jacs.9b11313en_US
dc.identifier.issn0002-7863
dc.identifier.doi10.1021/jacs.9b11313
dc.identifier.urihttp://hdl.handle.net/10545/624524
dc.description.abstractThe dinuclear photo-oxidizing RuII complex [{Ru(TAP2)}2(tpphz)]4+ (TAP = 1,4,5,8- tetraazaphenanthrene, tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′- h:2′′′,3′′′-j]phenazine), 14+ is readily taken up by live cells localizing in mitochondria and nuclei. In this study, the two-photon absorption cross-section of 14+ is quantified and its use as a two-photon absorbing phototherapeutic is reported. It was confirmed that the complex is readily photo-excited using near infrared, NIR, light through two-photon absorption, TPA. In 2-D cell cultures, irradiation with NIR light at low power results in precisely focused photo-toxicity effects in which human melanoma cells were killed after 5 minutes of light exposure. Similar experiments were then carried out in human cancer spheroids that provide a realistic tumor model for the development of therapeutics and phototherapeutics. Using the characteristic emission of the complex as a probe, its uptake into 280 µm spheroids was investigated and confirmed that the spheroid takes up the complex. Notably TPA excitation results in more intense luminescence being observed throughout the depth of the spheroids, although emission intensity still drops off toward the necrotic core. As 14+ can directly photo-oxidize DNA without the mediation of singlet oxygen or other reactive oxygen species, photo-toxicity within the deeper, hypoxic layers of the spheroids was also investigated. To quantify the penetration of these phototoxic effects, 14+ was photo-excited through TPA at a power of 60 mW, which was progressively focused in 10 µm steps throughout the entire z-axis of individual spheroids. These experiments revealed that, in irradiated spheroids treated with 14+, acute and rapid photo-induced cell death was observed throughout their depth, including the hypoxic region.en_US
dc.description.sponsorshipEPSRC postdoctoral funding of SAA and AR (EP/M015572/1)en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.urlhttps://pubs.acs.org/doi/pdf/10.1021/jacs.9b11313en_US
dc.relation.urlhttp://eprints.whiterose.ac.uk/157376/
dc.subjectColloid and Surface Chemistryen_US
dc.subjectCatalysisen_US
dc.titleA dinuclear ruthenium(II) complex excited by near-infrared light through two-photon absorption induces phototoxicity deep within hypoxic regions of melanoma cancer spheroidsen_US
dc.typeArticleen_US
dc.identifier.eissn1520-5126
dc.contributor.departmentThe University of Derbyen_US
dc.identifier.journalJournal of the American Chemical Societyen_US
dc.identifier.pii10.1021/jacs.9b11313
dc.source.journaltitleJournal of the American Chemical Society
dcterms.dateAccepted2020-02-17
dc.author.detail786274en_US


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