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Nanoscale fluorescence optical imaging probes are paving the way for novel methods to sense and spot live molecular targets.[1] Various probes have been developed, including semiconductor quantum dots,[2] magnetofluorescent nanoparticles,[3] polymer conjugates,[4] nanocomplexes,[5] and gold nanoparticles (AuNPs).[6] The application of conventional fluorescent probes is limited because they generally display only modest fluorescence changes, thus providing insufficient resolution. The limited degree of resolution is mainly attributed to the low fluorescence-quenching efficiency and specificity of the probes. Therefore, a high quenching efficiency and specific recognition properties by the target biomolecules are essential for the development of supersensitive fluorescence-based probes. Among the diverse candidates, biocompatible AuNPs [7] offer a considerable advantage in obtaining optical images through their nearinfrared-fluorescence (NIRF) quenching properties. Chromophores in close proximity to AuNPs experience strong electronic interactions with the surface, which results in donation of excited electrons to the metal nanoparticles and almost perfect quenching of the fluorescence.[8] However, the use of AuNP probes for in vivo visual biomolecular detection and real-time fluorescence tomography remains to be explored.

Herein, we describe the development of a proteasesensitive self-and AuNP-quenched NIRF probe. Proteases—or their inhibitors—are mainly involved in cancer, inflammation, and vascular disease.[9] Sensitive, convenient, and accurate protease-detection systems constitute a crucial tool for the development …