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β-Galactosidase-Activatable Nile Blue-Based NIR Senoprobe for the Real-Time Detection of Cellular Senescence

[Image: see text] Cellular senescence is a stable cell cycle arrest in response to stress or other damage stimuli to maintain tissue homeostasis. However, the accumulation of senescent cells can lead to the progression of various senescence-related disorders. In this paper, we describe the developme...

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Detalles Bibliográficos
Autores principales: Lozano-Torres, Beatriz, García-Fernández, Alba, Domínguez, Marcia, Sancenón, Félix, Blandez, Juan F., Martínez-Máñez, Ramón
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850349/
https://www.ncbi.nlm.nih.gov/pubmed/36580602
http://dx.doi.org/10.1021/acs.analchem.2c04766
Descripción
Sumario:[Image: see text] Cellular senescence is a stable cell cycle arrest in response to stress or other damage stimuli to maintain tissue homeostasis. However, the accumulation of senescent cells can lead to the progression of various senescence-related disorders. In this paper, we describe the development of a β-galactosidase-activatable near-infrared (NIR) senoprobe, NBGal, for the detection of senescent cells based on the use of the FDA-approved Nile blue (NB) fluorophore. NBGal was validated in chemotherapeutic-induced senescence cancer models in vitro using SK-Mel 103 and 4T1 cell lines. In vivo monitoring of cellular senescence was evaluated in orthotopic triple-negative breast cancer-bearing mice treated with palbociclib to induce senescence. In all cases, NBGal exhibited a selective tracking of senescent cells mainly ascribed to the overexpressed β-galactosidase enzyme responsible for hydrolyzing the NBGal probe generating the highly emissive NB fluorophore. In this way, NBGal has proven to be a qualitative, rapid, and minimally invasive probe that allows the direct detection of senescent cells in vivo.