Theranostics 2015; 5(8):787-795. doi:10.7150/thno.11139

Research Paper

A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging

Yaping Wang1,2, Tingting Lin1,2, Wenyuan Zhang2, Yifan Jiang2, Hongyue Jin2, Huining He1, Victor C. Yang1,3, Yi Chen2, Yongzhuo Huang2✉

1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
3. University of Michigan, College of Pharmacy, 428 Church St, Ann Arbor, MI 48108, USA.


Tumor-associated proteases (TAPs) have been intensively studied because of their critical roles in cancer development. As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers. Here we present a prodrug-type, MMP-2-responsive nanoprobe system with high efficiency and low toxicity for detecting MMP-2-overexpressed tumors. The nanoprobe system is featured by its self-assembled fabrication and FRET effect. This prodrug-type nanoprobe is selectively activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed cells and tumors. The nanoprobe system works successfully in various animal tumor models, including human fibrosarcoma and subcutaneous glioma xenograft. Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is strategically incorporated into the nanoprobe. The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging. This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).

Keywords: matrix metalloprotease, protease-activatable probe, tumor imaging, brain tumor, fluorescence resonance energy transfer.

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How to cite this article:
Wang Y, Lin T, Zhang W, Jiang Y, Jin H, He H, Yang VC, Chen Y, Huang Y. A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging. Theranostics 2015; 5(8):787-795. doi:10.7150/thno.11139. Available from