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β-Galactosidase-Triggered Photodynamic Elimination of Senescent Cells with a Boron Dipyrromethene-Based Photosensitizer
Adv Sci (Weinh). 2024 Jun 17:e2401012. doi: 10.1002/advs.202401012.
Jacky C H Chu 1, Blanca Escriche-Navarro 2 3 4 5, Junlong Xiong 1 6, Alba García-Fernández 2 4 5, Ramón Martínez-Máñez 2 3 4 5, Dennis K P Ng 1
Abstract:
...A β-galactosidase (β-gal)-activated boron dipyrromethene (BODIPY)-based photosensitizer (compound 1) is reported here that can selectively detect and eradicate senescent cells. It contains a galactose moiety connected to a pyridinium BODIPY via a self-immolative nitrophenylene linker, of which the photoactivity is effectively quenched. Upon interactions with the senescence-associated β-gal, it undergoes enzymatic hydrolysis followed by self-immolation, leading to the release of an activated BODIPY moiety by which the fluorescence emission and singlet oxygen generation are restored. The ability of 1 to detect and eliminate senescent cells is demonstrated in vitro and in vivo, using SK-Mel-103 tumor-bearing mice treated with senescence-inducing therapy. The results demonstrate that 1 can be selectively activated in senescent cells to trigger a robust senolytic effect upon irradiation. This study breaks new ground in the design and application of new senolytic agents based on photodynamic therapy.
PMID: 38884205
Free Full-Text: https://onlinelibrary.wiley.com/doi/10.1002/advs.202401012
Tags: beta-galactosidase, BODIPY, Compound 1, senolytics