Cathespin B-Initiated Cypate Nanoparticle Formation for Tumor Photoacoustic Imaging.

Cathepsin B (CTSB) is a lysosomal protease that is overexpressed in the early stage of many cancer types. Precise evaluation of CTSB expression in vivo may provide a promising method for the early diagnosis of cancers. By virtue of the high-resolution PA imaging modality, a "smart" photoacoustic (PA) probe Cypate-CBT, which can self-assemble to cypate-containing nanoparticles in response to abundant GSH and CTSB inside tumor cells, was developed for the sensitive and specific detection of CTSB activity. Compared with unmodified Cypate, our probe Cypate-CBT exhibited a 4.9-fold or 4.7-fold PA signal enhancement in CTSB-overexpressing MDA-MB-231 cancer cells or tumors, respectively, revealing intracellular accumulation of the probe after CTSB-initiated self-assembly. We expect Cypate-CBT to be employed as an effective PA imaging agent for clinical diagnosis of cancer at early stages.