A dinuclear ruthenium(II) complex excited by near-infrared light through two-photon absorption induces phototoxicity deep within hypoxic regions of melanoma cancer spheroids
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Raza et al JACS 2019.pdf
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2021-02-17
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Authors
Raza, AhtashamArcher, Stuart A
Fairbanks, Simon D
Smitten, Kirsty L.
Botchway, Stanley W.
Thomas, Jim A
MacNeil, Sheila
Haycock, John W.
Affiliation
The University of DerbyIssue Date
2020-02-17
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The 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.Citation
Raza, 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.9b11313Publisher
American Chemical Society (ACS)Journal
Journal of the American Chemical SocietyDOI
10.1021/jacs.9b11313Additional Links
https://pubs.acs.org/doi/pdf/10.1021/jacs.9b11313http://eprints.whiterose.ac.uk/157376/
Type
ArticleLanguage
enISSN
0002-7863EISSN
1520-5126ae974a485f413a2113503eed53cd6c53
10.1021/jacs.9b11313