Fluorogenic Disassembly of Self-Quenched Near-Infrared Nanoparticles Enables Matrix Metalloproteinase Detection

There are few reports on the enzyme-controlled disassembly of self-quenched near-infrared (NIR) fluorescent nanoparticles that turn fluorescence on for specific detection/imaging of their activity in vitro and in vivo. Herein, we report the rational design of a new NIR probe 1 whose fluorescence signal was self-quenched upon reduction-controlled condensation and subsequent assembly of its nanoparticles (i.e., 1-NP). Subsequent disassembly of 1-NP by matrix metalloproteinase 2 (MMP-2) turned the fluorescence on. Employing this enzymatic strategy, we successfully applied 1-NP for NIR detection of MMP-2 in vitro and NIR imaging of MMP-2 activity in living cells. Moreover, we also applied 1-NP for specific NIR imaging of MMP-2 activity in MC38 tumors in nude mice. We envision that this NIR probe 1 might be further developed for tumor-targeted imaging in routine preclinical studies or even in patients in the future.