Cathespin B‐Initiated Cypate Nanoparticle Formation for Tumor Photoacoustic Imaging

• Published in: Angewandte Chemie International Edition Vol. 61; no. 5; pp. e202114766 - n/a
• Main Authors: Wang, Chenchen, Du, Wei, Wu, Chenfan, Dan, Shan, Sun, Miao, Zhang, Tong, Wang, Bin, Yuan, Yue, Liang, Gaolin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.01.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; Cancer; Cathepsin B; Cathepsin B - analysis; Cathepsin B - metabolism; Cell Line, Tumor; Chemistry; Chemistry, Multidisciplinary; Diagnosis; Humans; In vivo methods and tests; Medical imaging; Mice; Nanoparticles; Nanoparticles - chemistry; Neoplasms - diagnostic imaging; Photoacoustic imaging; Photoacoustic Techniques - methods; Physical Sciences; Science & Technology; Self-assembly; Tumor cells; Tumors; Nanoparticles; Self-assembly; INVASION; Photoacoustic imaging; Cathepsin B; EARLY-STAGE; FURIN; PROBE; CATHEPSIN-B; Cathepsin B
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202114766

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. A near‐infrared photoacoustic (PA) probe Cypate‐CBT was designed for specific imaging and real‐time tracking of cathespin B (CTSB) activity in CTSB‐overexpressing cells and tumors. After Cypate‐CBT entered into CTSB‐overexpressing cells, it underwent glutathione reduction and CTSB cleavage to generate cypate nanoparticles Cypate‐CBT‐NPs, which enhanced both the intensity and retention time of the PA signal in tumor sites.