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 (H 2 O 2 ) plays a crucial role as a signaling molecule within cells. The concentration of H 2 O 2 differs in inflammation, cancer, cardiovascular and cerebrovascular diseases and neurodegenerative diseases compared to normal tissue. Therefore, the accurate determination of H 2 O 2 is important for the diagnosis and understanding of pathogenesis of disease. However, to accurately determine H 2 O 2 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 H 2 O 2 . The findings indicate that the BHTZ probe has high sensitivity, low toxicity and high stability, and can be utilized to detect H 2 O 2 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 H 2 O 2 levels in vivo, but also broaden the potential applications of MOFs in biomedical research and diagnostics.