Dual NIR-II fluorescence and ratiometric photoacoustic imaging-guided metal-phenolic nanosheets for H2S-activatable synergistic therapy

Metal-organic frameworks (MOFs) based on nanomaterials have attracted attention for tumor microenvironment (TME)-responsive therapy. However, they lack intrinsic imaging capabilities to monitor drug release and predict therapeutic outcomes. Herein, metal-phenolic nanosheets (Cu/EA-MOF) with photoacoustic (PA) imaging property in the second near-infrared window were constructed to achieve diagnosis and treatment for H₂S-enriched tumors. Endogenous H₂S triggers the decomposition of Cu/EA-MOF into the ellagic acid (EA) and copper sulfide (Cu_2-xS), which can be used for chemotherapy and chemodynamic therapy, respectively. Moreover, EA can enhance the efficiency of chemodynamic therapy by boosting superoxide dismutase activity. Importantly, the degradation of Cu/EA-MOF can be indicated via the change of ratiometric PA signal intensity. Furthermore, the NIR-II fluorescent molecule benzobisthiadiazole (BBT) was further introduced into Cu/EA-MOF to investigate the degradation process and drug release. As a promising theranostic nanomaterial, Cu/EA/BBT-MOF is successfully used to achieve effective synergistic therapy and predict therapeutic outcomes.