Cathespin B-Initiated Cypate Nanoparticle Formation for Tumor Photoacoustic Imaging

  • Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202114766. doi: 10.1002/anie.202114766.
Chenchen Wang  1 Wei Du  2 Chenfan Wu  1 Shan Dan  3 Miao Sun  3 Tong Zhang  1 Bin Wang  4 Yue Yuan  1 Gaolin Liang  1  5
Affiliations
  • 1. Hefei National Laboratory of Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China.
  • 2. Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
  • 3. Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China.
  • 4. Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.
  • 5. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China.
Abstract

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.

Keywords
Cathepsin B; Nanoparticles; Photoacoustic imaging; Self-assembly.
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