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

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.