Theranostics 2014; 4(2):134-141. doi:10.7150/thno.7217

Research Paper

Visualization of Protease Activity In Vivo Using an Activatable Photo-Acoustic Imaging Probe Based on CuS Nanoparticles

Kai Yang1,2†, Lei Zhu2,3†, Liming Nie2, Xiaolian Sun2, Liang Cheng1, Chenxi Wu2, Gang Niu2, Xiaoyuan Chen2✉, Zhuang Liu1✉

1. Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China
2. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States
3. Center for Molecular Imaging and Translational Medicine School of Public Health, Xiamen University, Xiamen 361005, China
† These authors contributed equally to this work


Herein, we for the first time report a novel activatable photoacoustic (PA) imaging nano-probe for in vivo detection of cancer-related matrix metalloproteinases (MMPs). A black hole quencher 3 (BHQ3) which absorbs red light is conjugated to near-infrared (NIR)-absorbing copper sulfide (CuS) nanoparticles via a MMP-cleavable peptide linker. The obtained CuS-peptide-BHQ3 (CPQ) nano-probe exhibits two distinctive absorption peaks at 630 nm and 930 nm. Inside the tumor microenviorment where MMPs present, the MMP-sensitive peptide would be cleaved, releasing BHQ3 from the CuS nanoparticles, the former of which as a small molecule is then rapidly cleared out from the tumor, whereas the latter of which as large nanoparticles would retain inside the tumor for a much longer period of time. As the result, the PA signal at 680 nm which is contributed by BHQ3 would be quickly diminished while that at 930 nm would be largely retained. The PA signal ratio of 680 nm / 930 nm could thus serve as an in vivo indicator of MMPs activity inside the tumor. Our work presents a novel strategy of in vivo sensing of MMPs based on PA imaging, which should offer remarkably improved detection depth compared with traditional optical imaging techniques.

Keywords: Peptide, Photoacoustic imaging, Enzyme cleavage, Copper sulfide, MMPs detection.

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How to cite this article:
Yang K, Zhu L, Nie L, Sun X, Cheng L, Wu C, Niu G, Chen X, Liu Z. Visualization of Protease Activity In Vivo Using an Activatable Photo-Acoustic Imaging Probe Based on CuS Nanoparticles. Theranostics 2014; 4(2):134-141. doi:10.7150/thno.7217. Available from