Dual-Locked Near-Infrared Fluorescent Probes for Precise Detection of Melanoma via Hydrogen Peroxide-Tyrosinase Cascade Activation.

Activity-based near-infrared (NIR) fluorescent probes provide powerful tools for diagnosis of diseases. However, most of these probes suffer from low specificity due to "off-target" reaction. The dual-locked strategy, which utilizes two biomarkers as triggers, can increase the specificity and precision of diagnosis. Here, we report a dual-locked NIR probe, MB- m -borate , which releases fluorophore methylene blue ( MB ) after hydrogen peroxide-tyrosinase (H 2 O 2 -TYR) cascade activation. Both MB- m -borate and its intermediate MB- m -phenol (the product after H 2 O 2 activation) show almost nondetectable fluorescence. MB- m -borate exhibits "turn on" fluorescence upon H 2 O 2 -TYR cascade activation. The further live cell bioimaging results indicate that MB- m -borate only responds to melanoma cells, providing it as a robust probe for precise detection of melanoma. Finally, the probe is applied for the diagnosis of melanoma in vivo with a xenogeneic mouse model.