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Ultraviolet phototoxicity of upconversion nanoparticles illuminated with near-infrared light

Abstract

Recently introduced upconversion nanoparticles (UCNPs) have pushed the photodynamic therapy (PDT) treatment depth to the centimetre range by converting deeply-penetrating near-infrared (NIR) radiation to visible for photoexcitation of PDT drugs. Here we demonstrate that direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT. To this aim, core/shell UCNPs of the formula NaYF4:Yb3+Tm3+/NaYF4 featuring an enhanced band in the ultraviolet UV-A and UV-B spectral bands was rationally designed and synthesised. Coupling UCNPs to recombinant modules of Designed Ankyrin Repeat Protein (DARPin) fused to a fluorescent protein mCherry allowed target delivery of DARPin-mCherry/UCNP to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2/neu receptors, as confirmed by fluorescence microscopy. DARPin-mCherry/UCNPs were demonstrated to be phototoxic to SK-BR-3 cells under 975-nm laser irradiation at a dose of 900 J/cm2 due to the UV photoexcitation of endogenous photosensitizers and concomitant generation of reactive oxygen species. Lewis lung cancer mouse model was employed to demonstrate the feasibility of PDT using UCNP-mediated UV excitation of endogenous photosensitizers in the tumor tissue at a NIR dose of 1200 J/cm2. This study paves a way to explore and harness UV photoexcitation processes in deep tissues in vivo.

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Publication details

The article was received on 08 Jun 2017, accepted on 01 Sep 2017 and first published on 04 Sep 2017


Article type: Paper
DOI: 10.1039/C7NR04092J
Citation: Nanoscale, 2017, Accepted Manuscript
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    Ultraviolet phototoxicity of upconversion nanoparticles illuminated with near-infrared light

    K. Mironova, D. A. Khochenkov , A. N. Generalova, V. V. Rocheva , N. V. Sholina, A. Nechaev, V. Semchishen, S. M. Deyev, A. V. Zvyagin and E. Khaydukov, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR04092J

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