A Nonconsumptive Fluorescent Probe for Precise Detection of Hydrogen Peroxide in Nonalcoholic Fatty Liver Disease and Inflammation

Hydrogen peroxide (H₂O₂) plays a vital role in various physiological and pathological processes. Thus, fluorescent probes of H₂O₂ are powerful tools for the investigation of H₂O₂-related diseases. However, developing fluorescent probes that do not irreversibly consume H₂O₂ presents a significant challenge. In this work, we introduce carbonate ester as a nonconsumptive recognizing molecule to construct RES-6C as a novel fluorescent probe of H₂O₂. RES-6C exhibited a selective and sensitive turn-on fluorescence response to H₂O₂, enabling the detection of H₂O₂ in cells without disturbing the cellular redox status. RES-6C has been applied to study nonalcoholic fatty liver disease, revealing that peroxisomes and mitochondria contribute to H₂O₂ production to a similar extent during very-long-chain fatty acid metabolism for the first time. It has also enabled fluorescent imaging of H₂O₂ in the LPS-induced inflammation mouse model. Overall, RES-6C serves as a versatile tool to monitor H₂O₂ in tissues and in vivo, providing new insights into the design of probes for H₂O₂.