A lipid droplet-targeted multifunctional AIE-active fluorescent probe for hydrogen peroxide detection and imaging-guided photodynamic therapy

Recent developments of activatable photosensitizers (aPSs) invigorate photodynamic therapy by enhancing sensitivity towards cancer cells and avoiding constant phototoxicity. However, the diversity of activatable photosensitizers needs to be developed urgently. Hydrogen peroxide (H2O2), as a typical biomarker which overexpressed in tumor tissue, is an ideal promoter for selectively activating photosensitizers to restore their photosensitivity. Herein, we construct a new H2O2-activated photosensitizer DPP-BPYS based on diketoprrrolopyrrole (DPP), which can rapidly and specifically respond to H2O2 both in vitro and in vivo, and exhibit “turn-on” near-infrared fluorescence emission. The activated DPP-BPYS performs typical aggregation-induced emission (AIE) characteristics, a large Stokes shift (180 nm), strong fluorescence quantum yield and high singlet oxygen (1O2) generating capacity. More importantly, activated DPP-BPYS can target lipid droplets (LDs) in tumor cells to form aggregates, and effectively generate reactive oxygen species under white light irradiation to induce apoptosis of tumor cells. Consequently, this research provides a unique molecular tool for H2O2-activated photodynamic anticancer therapy.