A mart-responsive photoacoustic sensor based on metal-organic framework as bioreactor for in situ visualization of hydrogen sulfide and tracking of drug-induced liver injury by NIR-II imaging

Metformin is currently the most commonly used oral drug for the treatment of diabetes. However, excessive use can up-regulate hydrogen sulfide (H2S) levels in the liver, which subsequently leads to severe liver injury and hepatotoxicity. Therefore, using endogenous H2S as a target molecule of an intelligent triggering sensor, a nano-probe that can recognize H2S with high specificity, and achieve non-invasive and highly specific in situ second near-infrared (NIR-II) photoacoustic (PA) imaging of hepatotoxicity induced by metformin would be welcomed in the field. In this work, we designed and synthesized a smart-responsive PA sensor based on metal-organic framework as bioreactor to dynamically monitor the changes in H2S levels induced by metformin. Molecular sieve imidazole framework-8 (ZIF-8) was selected as the coating layer, and the unique pore size of ZIF-8 was used to improve the selectivity of the sensor to H2S. The designed CuOxNPs@MOFs sensor turned on the PA signal of the sensor in NIR-II by in situ sulfation with overexpressed endogenous H2S in injured liver tissues. More importantly, the changes in the PA signal could non-invasively monitor liver injury in real time and with high sensitivity. Utilizing the unique structure in the MOFs sensor to selective recognize H2S molecules, ultra-sensitive monitoring and PA imaging of H2S in vitro and in vivo were achieved.