An OFF-ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo

Abstract

[EN] A naphthalimide-based two-photon probe (AHGa) for the detection of cell senescence is designed. The probe contains a naphthalimide core, an L-histidine methyl ester linker, and an acetylated galactose bonded to one of the aromatic nitrogen atoms of the L-histidine through a hydrolyzable N-glycosidic bond. Probe AHGa is transformed into AH in senescent cells resulting in an enhanced fluorescent emission intensity. In vivo detection of senescence is validated in mice bearing tumor xenografts treated with senescence-inducing chemotherapy. ; The authors thank the financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R) and the Generalitat Valenciana (Project PROMETEOII/2014/047). B.L-T. is grateful to the Spanish Ministry of Economy for her PhD grant. I.G. thanks the Generalitat Valenciana for her PhD grant. A.B. thanks the Spanish Government for the financial support "Juan de la Cierva-Incorporacion". M.R. is grateful to "La Caixa" foundation for his PhD scholarship. Work in the M.S. group was funded by the CNIO and by grants from Spanish Ministry of Economy, the European Regional Development Fund (SAF project) the European Research Council (ERC Advanced Grant), and the Botin Foundation and Banco Santander (Santander Universities Global Division). D.M.-E. was funded by a "Ramon y Cajal" Programme Senior Grant and the "RETOS" National Programme for Research (MINECO), Cancer Research UK, and the CRUK Cambridge Centre Early Detection Programme. ; Lozano-Torres, B.; Galiana, I.; Rovira, M.; Garrido-García, EM.; Chaib, S.; Bernardos Bau, A.; Muñoz-Espín, D. (2017). An OFF-ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo. Journal of the American Chemical Society. 139(26):8808-8811. https://doi.org/10.1021/jacs.7b04985 ; S ; 8808 ; 8811 ; 139 ; 26