Boost highly efficient singlet oxygen generation and accelerate cancer cell apoptosis for photodynamic therapy by logically designed mitochondria targeted near-infrared AIEgens

The aggregation-induced emission photosensitizers (AIE-PSs) manifest a multitude of notable superiorities in terms of high specificity to organelles, high-efficient singlet oxygen (1O2) generation as well as enhanced fluorescence intensity, which provides a feasible approach to overcome the problems such as the insufficient generation of reactive oxygen species (ROS) caused by grave aggregation-induced quenching (ACQ) and the lack of specific targeting existing in traditional PSs, but extremely challenging. Herein, a series of near-infrared (NIR) AIE luminogens (AIEgens) for targeting mitochondrial was devised and synthesized by regulating the D-A intensity assembly molecular engineering, which fabricating a progressively stronger intermolecular charge transfer (ICT) state to accelerate highly effective intersystem crossing (ISC) of excited electrons by the synergistic effect of thiophene and quinolinium. Impressively, the optimal NIR AIE-PS (DTTVQ-OH) revealed excellent photostability, biocompatibility, precise mitochondria targeting, extremely high generation yield of 1O2 (4.9-fold that of Rose Bengal) and superior phototoxicity in living HepG2 cells. Furthermore, apoptosis assay and cell migration experiment further demonstrated that DTTVQ-OH could efficaciously restrain cell proliferation and induce/speed up cancer cell death. Moreover, DTTVQ-OH can selectively distinguish cancer cells and normal cells by difference of fluorescence intensity in high resolution without the assist of any extra targeting ligands. As a consequence, this work provides a rational and practicable strategy for the specific targeted molecular engineering of AIE-PSs, which gives impetus to the development of fluorescence imaging-guided photodynamic therapy fields.