Targeted Delivery of γ-Glutamyl Transpeptidase-Activatable Near-Infrared Fluorescence Probe for Selective Cancer Imaging.

Research paper by Zhiliang Z Luo, Zheng Z Huang, Ke K Li, Yidan Y Sun, Jianguo J Lin, Deju D Ye, Hong-Yuan HY Chen

Indexed on: 30 Jan '18Published on: 30 Jan '18Published in: Analytical Chemistry


Non-invasive and specific detection of cancer cells in living subjects have been essential for the success of cancer diagnosis and treatment. Herein, we reported a strategy of combining a αvβ3 integrin receptor-targetable ligand c-RGD with γ-glutamyl transpep-tidase (GGT)-recognitive substrate γ-glutamate (γ-Glu) to develop a tumor targeting and GGT-activatable near-infrared (NIR) fluorescence probe for non-invasive imaging of tumors in living mice. We demonstrated that the probe was fluorescence off initial-ly, but the γ-Glu in the probe was specifically cleaved by GGT, releasing fluorescent product that could be selectively taken up by U87MG tumor cells via the αvβ3 receptor-mediated endocytosis. Remarkably enhanced intracellular NIR fluorescence distributed mainly the lysosomes was observed in the tumor cells only, capable of differentiating the tumor cells from GGT-positive but αvβ3-deficient normal cells. Moreover, the probe also showed a high selectivity for the real-time and non-invasive detection of GGT activity in the xenograft U87MG tumors following i.v. administration. This study reveals the advantage of using a combination of receptor-mediated cell uptake with molecular target-triggered activation to design molecular probes for improved cancer imaging, which could facilitate the effective cancer diagnosis.