Nitroreductase-Triggered Fluorophore Labeling of Cells and Tissues under Hypoxia.
Yun Jae YangYun Lim JungAnushree ShilSourav SarkarKyo Han AhnPublished in: Analytical chemistry (2024)
Several reductases, including nitroreductase, are upregulated under hypoxic conditions characterized by an oxygen-deficient microenvironment. Given that hypoxia is a prominent feature of solid tumors, our investigation focused on developing a bioconjugative probe designed for staining tissue under hypoxic conditions, particularly activated by nitroreductase. This probe, developed using our trigger-release-bioconjugation system rooted in the ortho -quinone methide chemistry, exhibited selective activation by nitroreductase and fluorophore labeling within mitochondria and endoplasmic reticulum. As a result, it displayed sustained fluorescence that persisted even after washing steps in cells and tissues. We applied this innovative probe to stain mouse kidney tissue in an acute kidney injury model induced by inadequate oxygen supply. Among various organ tissues examined, only kidney tissue showed significantly higher fluorescence in the injury model compared with the control tissue, as revealed by two-photon microscopic imaging. This research presents a promising avenue for the development of practical staining agents for image-guided tumor surgery.
Keyphrases
- endoplasmic reticulum
- induced apoptosis
- living cells
- acute kidney injury
- gene expression
- fluorescent probe
- cell cycle arrest
- quantum dots
- minimally invasive
- stem cells
- high resolution
- single molecule
- cardiac surgery
- signaling pathway
- oxidative stress
- deep learning
- reactive oxygen species
- percutaneous coronary intervention
- drug discovery