β-Galactosidase-Activatable Nile Blue-Based NIR Senoprobe for the Real-Time Detection of Cellular Senescence.
Beatriz Lozano-TorresAlba García-FernándezMarcia DomínguezFelix SancenónJuan F BlandezRamón Martínez-MáñezPublished in: Analytical chemistry (2022)
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 .
Keyphrases
- cell cycle arrest
- induced apoptosis
- cell death
- dna damage
- endothelial cells
- pi k akt
- minimally invasive
- stress induced
- fluorescent probe
- loop mediated isothermal amplification
- oxidative stress
- endoplasmic reticulum stress
- squamous cell carcinoma
- photodynamic therapy
- fluorescence imaging
- cell proliferation
- adipose tissue
- real time pcr
- sensitive detection
- drug induced