A Dual-Locked β‑Galactosidase/pH Near-Infrared Sensor Enables High-Fidelity Monitoring of Therapy-Induced Senescence.
- 1School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract
Therapy-induced senescence is increasingly recognized as a critical determinant of chemotherapy efficacy, tissue toxicity, and senolytic intervention. However, conventional senescence-associated β-galactosidase (SA-β-Gal) assays and single β-Gal-responsive probes often suffer from limited specificity because elevated β-Gal activity is not exclusive to senescent cells. Here, we report ECD-Gal, a dual-locked near-infrared fluorescent sensor that integrates β-Gal enzymatic activity with lysosomal pH variation for high-fidelity sensing therapy-induced senescence. ECD-Gal shows weak emission in β-Gal positive cells with an acidic lysosomal microenvironment but is strongly activated in senescent cells where β-Gal accumulation coincides with lysosomal alkalinization. Mechanistic studies using agents that induced lysosomal acidification or lysosomal alkalinization supported that both β-Gal activity and elevated lysosomal pH are required for fluorescence activation. ECD-Gal enabled confocal imaging, flow-cytometric quantification, in vivo visualization of doxorubicin or bleomycin-induced senescence, and its fluorescence readout correlated with SA-β-Gal staining, senescence marker expression, and fibrosis-associated pathological remodeling. This dual-locked sensing strategy provides a robust molecular tool for monitoring therapy-induced senescence and evaluating senolytic interventions in living systems.
Related
- Respiratory function monitoring during neonatal resuscitation: a crossover study of high-fidelity simulated bronchopulmonary dysplasia.
- A dendritic β-galactosidase-responsive folate–monomethylauristatin E conjugate
- Integrated multiclass driver ctDNA profiling enables MPNST detection and monitoring in NF1 patients
- Wastewater metagenomic sequencing enables broad pathogen and resistome monitoring in Lagos, Nigeria
- Serial Static Infrared Thermography for Intraoperative and Postoperative Surface-Temperature Monitoring of Free-Flap Skin Islands in Paediatric Craniofacial Reconstruction: A Technical Feasibility Study
BibTeX
@article{ding2026duallocked,
title = {{A Dual-Locked β‑Galactosidase/pH Near-Infrared Sensor Enables High-Fidelity Monitoring of Therapy-Induced Senescence.}},
author = {Lele Ding and Yuxuan Zhang and Na Wang and Zijian Li and Lijun Jia},
journal = {JACS Au},
year = {2026},
month = sep,
doi = {10.1021/jacsau.6c01028},
url = {https://europepmc.org/article/MED/42953165},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Dual-Locked β‑Galactosidase/pH Near-Infrared Sensor Enables High-Fidelity Monitoring of Therapy-Induced Senescence.
AU - Lele Ding
AU - Yuxuan Zhang
AU - Na Wang
AU - Zijian Li
AU - Lijun Jia
PY - 2026
DA - 2026/09/22
JO - JACS Au
DO - 10.1021/jacsau.6c01028
UR - https://europepmc.org/article/MED/42953165
AB - Therapy-induced senescence is increasingly recognized as a critical determinant of chemotherapy efficacy, tissue toxicity, and senolytic intervention. However, conventional senescence-associated β-galactosidase (SA-β-Gal) assays and single β-Gal-responsive probes often suffer from limited specificity because elevated β-Gal activity is not exclusive to senescent cells. Here, we report ECD-Gal, a dual-locked near-infrared fluorescent sensor that integrates β-Gal enzymatic activity with lysosomal pH variation for high-fidelity sensing therapy-induced senescence. ECD-Gal shows weak emission in β-Gal positive cells with an acidic lysosomal microenvironment but is strongly activated in senescent cells where β-Gal accumulation coincides with lysosomal alkalinization. Mechanistic studies using agents that induced lysosomal acidification or lysosomal alkalinization supported that both β-Gal activity and elevated lysosomal pH are required for fluorescence activation. ECD-Gal enabled confocal imaging, flow-cytometric quantification, in vivo visualization of doxorubicin or bleomycin-induced senescence, and its fluorescence readout correlated with SA-β-Gal staining, senescence marker expression, and fibrosis-associated pathological remodeling. This dual-locked sensing strategy provides a robust molecular tool for monitoring therapy-induced senescence and evaluating senolytic interventions in living systems.
SN - 2691-3704
ER -