Mitochondria-Targeted Fluorescent and Photoacoustic Imaging of Hydrogen Peroxide in Inflammation.

Abstract

Hydrogen peroxide (H2O2) is a prominent reactive oxygen species with relative stability, which makes it a potential diagnostic marker for pathological states. Excessive H2O2 in mitochondria leads to oxidative stress and inflammation. However, precisely monitoring the level of H2O2 at specific organelles (e.g., mitochondria) in vivo is still of urgent necessity. Therefore, we rationally designed a mitochondria-targeted near-infrared probe TPP-HCy-BOH for fluorescent/photoacoustic (FL/PA) dual-modal imaging of overproduced H2O2 in an inflamed mouse model. TPP-HCy-BOH had a low LOD (0.348 μM), which is comparable to those of recently reported probes for H2O2 detection. The high kinetic rate constant (kobs = 4.72 × 10-3 s-1) of TPP-HCy-BOH toward H2O2 is superior to recently reported H2O2 probes. Compared to control probe HCy-BOH without the mitochondrial targeting moiety, TPP-HCy-BOH successfully images exogenous or endogenous H2O2 in mitochondria with an additional 2.4-fold FL increase and 4.7-fold PA increase in HeLa cells or additional 2.1-fold FL increase and 3.3-fold PA increase in RAW 264.7 cells. In LPS-induced acute inflammation in vivo, TPP-HCy-BOH is more competent to image overproduced H2O2 with additional 1.6-fold higher sensitivity of FL in abdomen and 2.0-fold higher sensitivity of PA in liver and longer retention time of 0.5 h than HCy-BOH. We anticipate that TPP-HCy-BOH could be employed for the FL/PA dual-modal diagnosis of pathological inflammation in clinic in near future.

• Authors: Xiaoxia Chen, Xingxing Ren, Lele Zhang, Zhengjie Liu, Zijuan Hai
• Journal: Analytical chemistry (Anal Chem) Vol. 92 Issue 20 Pg. 14244-14250 (10 20 2020) ISSN: 1520-6882 [Electronic] United States
• PMID: 32985876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Carbocyanines
• Indicators and Reagents
• Organophosphorus Compounds
• Reactive Oxygen Species
• tetramethylene hemicyanine
• triphenylphosphine
• Hydrogen Peroxide

Topics

• Animals
• Biosensing Techniques
• Boronic Acids (chemistry)
• Carbocyanines (chemistry)
• HeLa Cells
• Humans
• Hydrogen Peroxide (metabolism)
• Indicators and Reagents (chemistry)
• Inflammation (diagnostic imaging)
• Mice
• Mitochondria (metabolism)
• Models, Animal
• Multimodal Imaging
• Optical Imaging (methods)
• Organophosphorus Compounds (chemistry)
• Oxidative Stress
• Photoacoustic Techniques (methods)
• RAW 264.7 Cells
• Reactive Oxygen Species (metabolism)
• Sensitivity and Specificity