Citation: He Yang, Xingkang Wu, Xianghui Lv, Fangjun Huo, Kaiqing Ma, Caixia Yin. A novel strategy: In situ real-time monitoring dual-mutant p53 based on sequential activable COX-2 fluorescent probe with high signal-to-background ratio[J]. Chinese Chemical Letters, ;2026, 37(11): 112204. doi: 10.1016/j.cclet.2025.112204 shu

A novel strategy: In situ real-time monitoring dual-mutant p53 based on sequential activable COX-2 fluorescent probe with high signal-to-background ratio

He Yang ^a ,
Xingkang Wu ^b ,
Xianghui Lv ^a ,
Fangjun Huo ^c ,
Kaiqing Ma ^{a, *,} ,
Caixia Yin ^{a, *,}

a.
Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
b.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
c.
Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China

makaiqing@sxu.edu.cn

yincx@sxu.edu.cn

Received Date: 3 November 2025
Revised Date: 27 November 2025
Accepted Date: 28 November 2025
Available Online: 30 November 2025

Figures(4)

Regarding the biological and clinical significance of in situ real-time detection of p53 dual mutations, this study ingeniously utilized the relationship between the genomic guardian p53 and the tumor promoter cyclooxygenase-2 (COX-2), attempting to develop a COX-2-activated fluorescence probe with cascade response for dual-mutant p53. We developed a novel class of fluorescent probes based on protected dihydroresorufin conjugated with a photo-crosslinking group. This design enables the sequential release of the fluorophore, effectively preventing over-oxidation and allowing for rapid detection of COX-2 activity with enhanced signal-to-background contrast in living cells. Furthermore, these probes can specific recognize dual-mutant p53 based on markedly elevated activity of COX-2 in SW480 cells compared to other colorectal cancer (CRC) cell lines with wild-type or mono-mutant p53 for the first time. This specifically recognition of the dual mutant p53 also enables its implementation in tissues and xenografts. Additionally, metabolomic profiling showed increased acylcarnitine levels in dual-mutant p53 SW480 cells, which could activate COX-2 and enhance prostaglandin E2 (PGE2) production. In situ real-time detection of dual-mutant p53 is of great significance for precise tumor diagnosis and grading, individualized treatment, prognosis judgment and recurrence monitoring, and new drug development.
- Fluorescent probe,
- Dihydroresorufin,
- COX-2,
- p53 mutation,
- Bioimaging,
- Acylcarnitine
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