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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Chu JCH
  • Xiong J
  • Wong CTT
  • Wang S
  • Tam DY
  • García-Fernández A
  • Ng DKP

Grupos

Abstract

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 µM.

Datos de la publicación

ISSN/ISSNe:
0022-2623, 1520-4804

JOURNAL OF MEDICINAL CHEMISTRY  American Chemical Society

Tipo:
Article
Páginas:
234-244
PubMed:
38113190
Factor de Impacto:
1,888 SCImago
Cuartil:
Q1 SCImago

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Keywords

  • PHOTODYNAMIC THERAPY; CELLULAR SENESCENCE; FLUORESCENT-PROBE; PHOTOSENSITIZER; PHTHALOCYANINES; NANOPARTICLES; STRATEGIES; ABLATION

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