In vivo imaging of caspase-1 activation enables efficient and rapid detection of various inflammatory disorders

Abstract Inflammasome plays a critical role in diverse inflammatory diseases, including cancers and Alzheimer’s disease. It can be activated by a various stimuli and induces secretion of IL-1β after cleavage by active caspase-1, an executing enzymatic component of the inflammasome complex. Therefore, direct imaging of active caspase-1 in vivo may provide enormous advantages for diagnosis, drug discovery, and therapeutic monitoring in various inflammatory disorders. Here, we developed a new imaging probe for in vivo visualization of active caspase-1. For this, we synthesized a caspase-1-specific cleavable peptide bridging a near-infrared (NIR) fluorescence (Cy5.5) dye and a hydrophobic quencher. This novel caspase-1 probe can be efficiently delivered into cells and specifically emit fluorescence upon caspase-1 activation as measured by in vitro and in vivo inflammatory models. We demonstrated efficient in vivo imaging of caspase-1 activation in early stage of various inflammatory conditions in mice models, including endotoxin stimulation, inflammatory bowel disorder, transplanted cancer, and Alzheimer’s disease. Efficient and rapid detection of caspase-1 activity in vivo can revolutionize the current paradigm for diagnosis and therapeutics in various inflammatory disorders.