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    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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    Name:
    Raza et al JACS 2019.pdf
    Embargo:
    2021-02-17
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    2.289Mb
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    Authors
    Raza, Ahtasham
    Archer, Stuart A
    Fairbanks, Simon D
    Smitten, Kirsty L.
    Botchway, Stanley W.
    Thomas, Jim A
    MacNeil, Sheila
    Haycock, John W.
    Affiliation
    The University of Derby
    Issue Date
    2020-02-17
    
    Metadata
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    Abstract
    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.9b11313
    Publisher
    American Chemical Society (ACS)
    Journal
    Journal of the American Chemical Society
    URI
    http://hdl.handle.net/10545/624524
    DOI
    10.1021/jacs.9b11313
    Additional Links
    https://pubs.acs.org/doi/pdf/10.1021/jacs.9b11313
    http://eprints.whiterose.ac.uk/157376/
    Type
    Article
    Language
    en
    ISSN
    0002-7863
    EISSN
    1520-5126
    ae974a485f413a2113503eed53cd6c53
    10.1021/jacs.9b11313
    Scopus Count
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