Rational design of biomimetic-inspired nanoenzyme probes based on metal-organic frameworks (MOFs) for NIR-II window photoacoustic imaging of ultra-trace H2O2 activation in vivo

Hydrogen peroxide (H2O2) plays a crucial role as a signaling molecule within cells. The concentration of H2O2 differs in inflammation, cancer, cardiovascular and cerebrovascular diseases and neurodegenerative diseases compared to normal tissue. Therefore, the accurate determination of H2O2 is important for the diagnosis and understanding of pathogenesis of disease. However, to accurately determine H2O2 levels in vivo, highly sensitive biosensors and deep tissue penetrating imaging techniques are required. To address this challenge, we developed a biocatalytic porous structure composed of metal-organic frameworks (MOFs) that encapsulates horseradish peroxidase (HRP) and 3, 3 ', 5, 5 '-Tetramethylbenzidine (TMB) in situ, enabling biomineralization while maintaining the catalytic activity and stability of natural enzymes. This leads to the formation of a hypersensitive biological probe BSA@HRP@TMB@ZIF-8 (BHTZ). BHTZ is an activatable near-infrared probe and its absorption signal in the second near-infrared window (1030 nm) is activated in the presence of H2O2. The findings indicate that the BHTZ probe has high sensitivity, low toxicity and high stability, and can be utilized to detect H2O2 levels in mice with drug-induced liver injury, such as that caused by lipopolysaccharide (LPS) in vivo. These results not only provide a highly sensitive and deep imaging method for monitoring physiological changes in H2O2 levels in vivo, but also broaden the potential applications of MOFs in biomedical research and diagnostics.