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 <b>RES-6C</b> as a novel fluorescent probe of H₂O₂. <b>RES-6C</b> exhibited a selective and sensitive turn-on fluorescence response to H₂O₂, enabling the detection of H₂O₂ in cells without disturbing the cellular redox status. <b>RES-6C</b> 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, <b>RES-6C</b> serves as a versatile tool to monitor H₂O₂ in tissues and <i>in vivo</i>, providing new insights into the design of probes for H₂O₂.