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Color-Convertible, Unimolecular, Micelle-Based, Activatable Fluorescent Probe for Tumor-Specific Detection and Imaging In Vitro and In Vivo.

Recent years have witnessed significant progress in molecular probes for cancer diagnosis. However, the conventional molecular probes are designed to be "always-on" by attachment of tumor-targeting ligands, which limits their abilities to diagnose tumors universally due to the variations of targeting efficiency and complex environment in different cancers. Here, it is proposed that a color-convertible, activatable probe is responding to a universal tumor microenvironment for tumor-specific diagnosis without targeting ligands. Based on the significant hallmark of up-regulated hydrogen peroxide (H2 O2 ) in various tumors, a novel unimolecular micelle constructed by boronate coupling of a hydrophobic hyperbranched poly(fluorene-co-2,1,3-benzothiadiazole) core and many hydrophilic poly(ethylene glycol) arms is built as an H2 O2 -activatable fluorescent nanoprobe to delineate tumors from normal tissues through an aggregation-enhanced fluorescence resonance energy transfer strategy. This color-convertible, activatable nanoprobe is obviously blue-fluorescent in various normal cells, but becomes highly green-emissive in various cancer cells. After intravenous injection to tumor-bearing mice, green fluorescent signals are only detected in tumor tissue. These observations are further confirmed by direct in vivo and ex vivo tumor imaging and immunofluorescence analysis. Such a facile and simple methodology without targeting ligands for tumor-specific detection and imaging is worthwhile to further development.