Cellular senescence imaging and senolysis monitoring in cancer therapy based on a β-galactosidase-activated aggregation-induced emission luminogen

作者：Peili Cen, Chunyi Cui, Jiani Huang, Hetian Chen, Fei Wu, Jiaqi Niu, Yan Zhong, Chentao Jin, Weihong Zhu, Hong Zhang, Mei Tian · 发表于：Acta Biomaterialia · 年份：2024 · DOI：10.1016/j.actbio.2024.03.027 · 被引用次数：21 · 研究领域：Nanoplatforms for cancer theranostics、Luminescence and Fluorescent Materials、Advanced biosensing and bioanalysis techniques

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated β-galactosidase (SA-β-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting β-galactosidase (β-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with β-Gal-responsive capabilities. In this study, we introduced a β-Gal-activated AIEgen named QM-β-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-β-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon β-Gal activation. It showed high specificity towards the activity of β-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-β-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the ...