Design and synthesis of a novel chiral photoacoustic probe and accurate imaging detection of hydrogen peroxide in vivo.

Nanocatalytic medicine, which aims to accurately target and effectively treat tumors through intratumoral in situ catalytic reactions triggered by tumor-specific environments or markers, is an emerging technology. However, the relative lack of catalytic activity of nanoenzymes in the tumor microenvironment (TME) has hampered their use in biomedical applications. Therefore, it is crucial to develop a highly sensitive probe that specifically responds to the TME or disease markers in the TME for precision diagnosis and treatment of diseases. In this work, a chiral photoacoustic (PA) nanoprobe (D/L-Ce@MoO) based on the HO-catalyzed TME activation reaction was constructed in a one-step method using D-cysteine (D-Cys) or L-cysteine (L-Cys), polymolybdate, and cerium nitrate as raw materials. The designed and synthesized D/L-Ce@MoO chiral nanoprobe can perform in situ, non-invasive, and precise imaging of pharmacological acute liver injury. In vivo and in vitro experiments have shown that the D/L-Ce@MoO probe had chiral properties, the CD signal decreased upon reaction with HO, and the absorption and PA signals increased with increasing HO concentration. This is because of the catalytic reaction between Ce ions doped in the nanoenzyme and the high expression of HO caused by drug-induced liver injury to produce ·OH, which has a strong oxidizing property to kill tumor cells and destroy the Mo-S bond in the probe, thus converting the chiral probe into an achiral polyoxometalate (POM) with PA signal.