Synchronous detection of glutathione/hydrogen peroxide for monitoring redox status in vivo with a ratiometric upconverting nanoprobe
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Cellular redox status presents broad implications with diverse physiological and pathological processes. Simultaneous detection of both the oxidative and reductive species of redox couples, especially the most representative pair glutathione/hydrogen peroxide (GSH/H2O2), is crucial to accurately map the cellular redox status. However, it still remains challenging to synchronously detect GSH/H2O2in vivo due to lack of a reliable measuring tool. Herein, a ratiometric nanoprobe (UCNP-TB) possessing simultaneous delectability of GSH/H2O2 is established based on a multi-spectral upconverting nanophosphor (UCNP-OA) as the luminescence resonance energy transfer (LRET) donor and two dye molecules as the acceptors, including a GSH-sensitive dye (TCG) and a H2O2-sensitive dye (BCH). With the as-prepared UCNP-TB, real-time and synchronous monitoring the variation of GSH and H2O2in vitro and in living mice can be achieved using the ratio of the upconversion luminescence (UCL) at 540 and 650 nm to that at 800 nm as the detection signal, respectively, providing highly inherent reliability of the sensing results by self-calibration. Moreover, the nanoprobe is capable of mapping the redox status within the drug-resistant tumor and the drug-induced hepatotoxic liver via ratiometric UCL imaging. Thus, this nanoprobe would provide a reliable tool to elucidate the redox state in vivo.
Keywordsredox status glutathione hydrogen peroxide upconversion imaging nanoprobe
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This research was supported by the National Natural Science Foundation of China (Nos. 21771065 and 81630046), the Natural Science Foundation of Guangdong Province, China (No. 2017A020215088), the Science and Technology Planning Project of Guangdong Province, China (Nos. 2015B020233016 and 2014B020215003), the Science and Technology Planning Project of Guangdong Province (Guangdong-Hong Kong Joint Innovation Project), China (No. 2014B050504009) Pearl River Nova Program of Guangzhou, Guangdong Province, China (No. 201806010189), and the Scientific and Technological Planning Project of Guangzhou, Guangdong Province, China (No. 201805010002).
- Breckwoldt, M. O.; Pfister, F. M. J.; Bradley, P. M.; Marinkovic, P.; Williams, P. R.; Brill, M. S.; Plomer, B.; Schmalz, A.; St Clair, D. K.; Naumann, R. et al. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Nat. Med. 2014, 20, 555–560.CrossRefGoogle Scholar
- Ishimoto, T.; Nagano, O.; Yae, T.; Tamada, M.; Motohara, T.; Oshima, H.; Oshima, M.; Ikeda, T.; Asaba, R.; Yagi, H. et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc–and thereby promotes tumor growth. Cancer Cell 2011, 19, 387–400.CrossRefGoogle Scholar
- McMahon, B. K.; Gunnlaugsson, T. Selective detection of the reduced form of glutathione (GSH) over the oxidized (GSSG) form using a combination of glutathione reductase and a Tb(III)-cyclen maleimide based lanthanide luminescent “switch on” assay. J. Am. Chem. Soc. 2012, 134, 10725–10728.CrossRefGoogle Scholar
- Zhou, Y.; Pei, W. B.; Wang, C. Y.; Zhu, J. X.; Wu, J. S.; Yan, Q. Y.; Huang, L.; Huang, W.; Yao, C.; Loo, J. S. C. et al. Rhodamine-modified upconversion nanophosphors for ratiometric detection of hypochlorous acid in aqueous solution and living cells. Small 2014, 10, 3560–3567.CrossRefGoogle Scholar
- Xiao, Q. F.; Zheng, X. P.; Bu, W. B.; Ge, W. Q.; Zhang, S. J.; Chen, F.; Xing, H. Y.; Ren, Q. G.; Fan, W. P.; Zhao, K. L. et al. A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. J. Am. Chem. Soc. 2013, 135, 13041–13048.CrossRefGoogle Scholar
- Peng, J. J.; Samanta, A.; Zeng, X.; Han, S. Y.; Wang, L.; Su, D. D.; Loong, D. T. B.; Kang, N. Y.; Park, S. J.; All, A. H. et al. Real-time in vivo hepatotoxicity monitoring through chromophore-conjugated photonupconverting nanoprobes. Angew. Chem., Int. Ed. 2017, 56, 4165–4169.CrossRefGoogle Scholar
- Harris, I. S.; Treloar, A. E.; Inoue, S.; Sasaki, M.; Gorrini, C.; Lee, K. C.; Yung, K. Y.; Brenner, D.; Knobbe-Thomsen, C. B.; Cox, M. A. et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 2015, 27, 211–222.CrossRefGoogle Scholar
- Szatrowski, T. P.; Nathan, C. F. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991, 51, 794–798.Google Scholar
- Jiang, X. Q.; Yu, Y.; Chen, J. W.; Zhao, M. K.; Chen, H.; Song, X. Z.; Matzuk, A. J.; Carroll, S. L.; Tan, X.; Sizovs, A. et al. Quantitative imaging of glutathione in live cells using a reversible reaction-based ratiometric fluorescent probe. ACS Chem. Biol. 2015, 10, 864–874.CrossRefGoogle Scholar