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

[EN] Senescent cells have become an important therapeutic target for many age-related dysfunctions and diseases. We report herein a novel nanophotosensitizing system that is responsive to the senescence-associated ß-galactosidase (ß-gal) for selective detection and elimination of these cells. It inv...

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Detalles Bibliográficos
Autores: Chu, Jacky C. H., Xiong, Junlong, Wong, C.T.T., Wang, S., Tam, D.Y., Ng, Dennis K. P., García-Fernández, Alba|||0000-0002-8416-1674, Martínez-Máñez, Ramón|||0000-0001-5873-9674
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/227146
Acceso en línea:https://riunet.upv.es/handle/10251/227146
Access Level:acceso abierto
Palabra clave:Senescent Cells
Dimeric zinc
Dysfunctions
Descripción
Sumario:[EN] Senescent cells have become an important therapeutic target for many age-related dysfunctions and diseases. We report herein a novel nanophotosensitizing system that is responsive to the senescence-associated ß-galactosidase (ß-gal) for selective detection and elimination of these cells. It involves a dimeric zinc(II) phthalocyanine linked to a ß-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 ß-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 ¿M.