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

Abstract

Senescent cells have become an important therapeutic target for many agerelated dysfunctions and diseases. We report herein a novel nanophotosensitizing system that is responsive to the senescence-associated β-galactosidase (β-gal) for selective detection and elimination of these cells. It involves a dimeric zinc(II) phthalocyanine linked to a β-galactose unit via a self-immolative linker. This compound can self-assemble in aqueous media, forming stable nanoscale particles in which the phthalocyanine units are stacked and self-quenched for fluorescence emission and singlet oxygen production. Upon internalization into senescent HeLa cells, these nanoparticles interact with the overproduced senescence-associated β-gal inside the cells to trigger the disassembly process through enzymatic cleavage of the glycosidic bonds, followed by self-immolation to release the photoactive monomeric phthalocyanine units. These senescent cells can then be lit up with fluorescence and eliminated through the photodynamic action upon light irradiation with a half-maximal inhibitory concentration of 0.06 μM.

Self-Immolative Domino Dendrimers as Anticancer-Drug Delivery Systems: A Review

“…Unfortunately, a particular disadvantage is this system's very complicated synthesis method. Chu et al have developed an interesting nanophotosensitizing approach of SIDendr with a high potential for use in cancer therapy (Figure 21) [32]. This novel system responds to the senescence-associated β-galactosidase (β-gal) to detect and eliminate cancer cells selectively.…”

“…This is followed by self-immolation to release the photoactive monomeric phthalocyanine moieties. Fluorescence can light up these senescent cells and eliminate them through photodynamic action when irradiated with light [32]. The nanosystem can serve as an efficient fluorescent probe for detecting cellular senescence, due to the 4.5-fold higher intensity of the fluorescence in the senescent cells compared to the proliferating cells.…”

“…The nanosystem can serve as an efficient fluorescent probe for detecting cellular senescence, due to the 4.5-fold higher intensity of the fluorescence in the senescent cells compared to the proliferating cells. It is also possible to activate the intracellular ROS generation ability, enabling the effective killing of the senescent cells with an IC 50 value as low as 0.06 µM [32].…”