Lipid Droplet‐Targetable Fluorescence Guided Photodynamic Therapy of Cancer Cells with an Activatable AIE‐Active Fluorescent Probe for Hydrogen Peroxide

Abstract Fluorescence guided photodynamic therapy (FL‐PDT) offers the great opportunity for realizing personalized medicine in the treatment of cancer. Aggregation‐induced emission luminogens (AIEgens) with efficient emission and reactive oxygen species (ROS) generation even in the aggregated state are the ideal FL‐PDT photosensitizers to overcome the quenched fluorescence and ROS that traditional photosensitizers faced in PDT. Moreover, considering the higher levels of H₂O₂ in cancer cells than in normal cells and the fact that lipid droplet (LD) accumulation correlates to the enhanced survival rate of cancer cells in hypoxic conditions, it will be very interesting and rewarding to develop a LD‐targeted, H₂O₂ activatable AIE‐active photosensitizer for FL‐PDT. Thereafter, a LD‐targeted fluorescent probe TPECNPB is fabricated for H₂O₂‐activatable fluorescence guided PDT of cancer cells. AIE‐active TPECNPB exhibits the unique features of large Stokes shift (175 nm), superior photostability, and excellent selectivity toward H₂O₂. TPECNPB is able to selectively accumulate in LD and is activated by endogenous H₂O₂ for light‐up bioimaging in live MCF‐7 cells. In addition, H₂O₂‐activatable singlet oxygen generation and PDT of cancer cells has also been successfully implemented with TPECNPB. These prominent parameters would make TPECNPB a powerful toolbox for H₂O₂‐activatable and LD‐targetable fluorescence guided PDT of cancer cells.