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Title: Bienzyme-locked activatable fluorescent probes for specific imaging of tumor-associated mast cells
Authors: Hu, Yuxuan
Yu, Jie
Xu, Mengke
Pu, Kanyi
Keywords: Engineering
Issue Date: 2024
Source: Hu, Y., Yu, J., Xu, M. & Pu, K. (2024). Bienzyme-locked activatable fluorescent probes for specific imaging of tumor-associated mast cells. Journal of the American Chemical Society, 146(18), 12656-12663.
Project: NRF-NRFI07-2021-0005 
Journal: Journal of the American Chemical Society 
Abstract: Tumor-associated mast cells (TAMCs) have been recently revealed to play a multifaceted role in the tumor microenvironment. Noninvasive optical imaging of TAMCs is thus highly desired to gain insights into their functions in cancer immunotherapy. However, due to the lack of a single enzyme that is specific to mast cells, a common probe design approach based on single-enzyme activation is not applicable. Herein, we reported a bienzyme-locked molecular probe (THCMC) based on a photoinduced electron transfer-intramolecular charge-transfer hybrid strategy for in vivo imaging of TAMCs. The bienzyme-locked activation mechanism ensures that THCMC exclusively turns on near-infrared (NIR) fluorescence only in the presence of both tryptase and chymase specifically coexpressed by mast cells. Thus, THCMC effectively distinguishes mast cells from other leukocytes, including T cells, neutrophils, and macrophages, a capability lacking in single-locked probes. Such a high specificity of THCMC allows noninvasive tracking of the fluctuation of TAMCs in the tumor of living mice during cancer immunotherapy. The results reveal that the decreased intratumoral signal of THCMC after combination immunotherapy correlates well with the reduced population of TAMCs, accurately predicting the inhibition of tumor growth. Thus, this study not only presents the first NIR fluorescent probe specific for TAMCs but also proposes a generic bienzyme-locked probe design approach for in vivo cell imaging.
ISSN: 0002-7863
DOI: 10.1021/jacs.4c02070
Schools: School of Chemistry, Chemical Engineering and Biotechnology 
Rights: © 2024 American Chemical Society. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at:
Fulltext Permission: embargo_20250506
Fulltext Availability: With Fulltext
Appears in Collections:CCEB Journal Articles

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