beta-Galactosidase-Triggered Photodynamic Elimination of Senescent Cells with a Boron Dipyrromethene-Based Photosensitizer.

Autores de IIS La Fe

• Blanca Escriche Navarro

  Autor

• Alba Garcia Fernandez

  Autor

• Ramón Martínez Máñez

  Autor

Participantes ajenos a IIS La Fe

• Chu, Jacky C H
• Xiong, Junlong
• Ng, Dennis K P

Grupos

• Unidad Mixta de Investigación en Nanomedicina y Sensores

  Leader

  Ramón Martínez Máñez

Abstract

Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age-related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge. A beta-galactosidase (beta-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 beta-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.

© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH.

Keywords

• boron dipyrromethene; photodynamic therapy; senescent cells; singlet oxygen; ß-galactosidase