Selective photodynamic eradication of senescent cells with a β-galactosidase-activated photosensitiser

Abstract

A β-galactosidase-responsive photosensitiser has been designed and synthesised. It contains a galactosyl substrate, a boron dipyrromethene-based photosensitising unit and a black hole quencher 2 connected via an AB2-type self-immolative linker....

Detection and Elimination of Senescent Cells with a Self-Assembled Senescence-Associated β-Galactosidase-Activatable Nanophotosensitizer

“…The results strongly suggest that Gal-(ZnPc*) 2 -NP is disassembled inside the senescent cells and activated by the senescence-associated β-gal therein, and these processes can be completed in about 4 h. Under these optimal incubation conditions, the fluorescence intensity of the senescent cells was about 4.5-fold higher than that of the proliferating cells. The enhancement was significantly larger than that observed using our previously reported BODIPY-based photosensitizer (3.1-fold) and the commercial probe C 12 FDG (2.5-fold), showing that this nanosystem behaved as a more efficient fluorescent probe for detecting cellular senescence. The stronger intracellular fluorescence in senescent cells caused by Gal-(ZnPc*) 2 -NP was also observed in their confocal images (Figure b).…”

“…Being encouraged by these results, we further examined the in vitro response of Gal-(ZnPc*) 2 -NP toward senescence-associated β-gal in senescent cells. The senescent-cell model was prepared according to our previously described procedure . In brief, HeLa human cervical adenocarcinoma cells were sequentially incubated with doxorubicin (50 nM) for 72 h and then in a drug-free medium for a further 24 h. The induced cellular senescence was then assessed using an X-Gal staining assay and the fluorogenic probe C 12 FDG .…”

“…Compound 1 contains a self-immolative AB 2 -type platform that can connect to various substrates and therapeutic components for controlled drug delivery . With a β-galactose terminal group, this compound is responsive toward β-gal and has been used by us previously for the construction of a β-gal-activatable photosensitizer . Both 2 and Gal-(ZnPc*) 2 were characterized with 1 H NMR spectroscopy and electrospray ionization (ESI) mass spectrometry.…”

“…For the latter, the bacterial β-gal expression is in the cell cytoplasm, while the β-gal activity is in the lysosomes for senescent cells. In fact, to the best of our knowledge, only three molecular senescence-associated β-gal-activatable photosensitizers have been reported so far, which include a methylene blue derivative reported by Yang and co-workers and Tung and co-workers independently, a selenium-containing naphthoquinone methide reported by Li and co-workers, and a boron dipyrromethene (BODIPY) reported by us recently …”

“…The use of nanoparticles can promote the self-quenching of the encapsulated photosensitizing molecules in the native form and lead to a more remarkable activation effect upon stimulus-triggered dissociation in the target cells. Compared with the aforementioned molecular systems, − this nanophotosensitizer exhibits much higher photocytotoxicity against the senescent cells.…”