An AIE photosensitizer with unquenched fluorescence based on nitrobenzoic acid for tumor-targeting and image-guided photodynamic therapy.

Fluorescence quenching occurs in most nitroaromatic compounds due to photoinduced electron transfer (PET) effects, limiting their use as image-guided photosensitizers for anticancer photodynamic therapy (PDT) or as probes for nitroreductase in hypoxic cells. Herein, we developed a tumor-targeting aggregation-induced emission photosensitizer (AIE-PS), Biotin-TTVBA, by binding TTVBA (a nitrobenzoic acid-based AIE-PS with a free carboxylic acid group) to biotin. Biotin-TTVBA has near-infrared emission characteristics in DMSO containing 99% toluene, a large Stoke's shift (210 nm), high photostability, wash-free cell staining ability and type I/II photosensitivity. Compared with TTVBA, Biotin-TTVBA significantly increased cellular uptake (a 60-fold increase) and selective uptake of tumor cells (a 250% increase in the ratio of tumor cells to normal cells), resulting in enhanced antitumor activity against tumor cells (HeLa and MCF-7) and a decreased IC 50 value (from >40 μM to 2.5 μM). Taken together, the results of this study call attention to AIE-PSs based on nitroaromatic groups because of their strong fluorescence and ROS generation ability, which can be used in image-guided photodynamic therapy and provide a new approach for tumor-targeting design of AIE-PSs.