Dipeptidylpeptidase-4-targeted activatable fluorescent probes visualize senescent cells.

Area of Science:

• Biomedical research
• Cancer biology
• Molecular imaging

Background:

• Senescent cells contribute to cancer progression via chronic inflammation and the senescence-associated secretory phenotype (SASP).
• Existing senotherapeutic strategies lack in vivo methods for detecting and evaluating senescent cell accumulation.

Purpose of the Study:

• To develop and validate a technology for the in vivo detection and evaluation of senescent cells.
• To identify effective fluorescent probes for visualizing senescent cells in living organisms.

Main Methods:

• Enzymatic activity-based screening of fluorescent probes.
• Identification of activatable fluorescent probes targeting dipeptidylpeptidase-4 (DPP4).
• In vivo imaging of senescent cells in mouse organs using DPP4-targeted probes.

Main Results:

• Activatable fluorescent probes targeting DPP4 were identified as effective for senescent cell detection.
• These probes demonstrated high selectivity and rapid activation in senescent cells during live imaging.
• Successful visualization of senescent cells in mouse organs was achieved using DPP4-targeted probes.

Conclusions:

• DPP4-targeted fluorescent probes offer a promising tool for in vivo senescent cell detection.
• This technology could lead to noninvasive diagnostic methods for senescent cell accumulation.
• The findings support the potential application of DPP4 prodrugs in senotherapy.