Dual-targeted and viscosity-sensitive infrared AIE photosensitizer based on tumor microenvironmental response for photodynamic cancer therapy†

Due to their excellent capabilities in photodynamic therapy (PDT) and aggregation-induced emission, (AIE) photosensitizers have attracted a great deal of attention. However, the poor water solubilities of current AIE photosensitizers limit their widespread in vivo application and PDT productivity. AIE photosensitizers with triphenylamine as electron-donating moiety and pyridine as electron-absorbing group can enhance the D–A effort, thus improving the intramolecular charge transfer (ICT) and extending the emission wavelength. At the same time, ΔE_st was reduced and intersystem crossing processes was promoted due to the D–A effect of the photosensitizers, thus increasing the probability of ROS generation. Herein, a dual-organelle targeted and viscosity-sensitive infrared AIE photosensitizer (NES-OH) with a D–A structure was developed and synthesized. The NES-OH had good water solubility and good linear relationship with concentration. The NES-OH exhibited bright fluorescence at 620 nm with a quantum yield of 66.75% and had high ¹O₂ generation efficiency, as well as good biocompatibility and photostability. The NES-OH can target mitochondria and lysosomes and also monitor lysosomes and mitochondrial viscosity changes in real time or in situ in living cells. More interestingly, in the acidic environment of cancer cells, the structure of the NES-OH changed with the appearance of specific morpholine groups, leading to the targeting of lysosomes and further distinguishing and detecting normal and cancer cells. The in vitro and in vivo study demonstrated that the NES-OH can inhibit tumor growth efficiently upon light exposure. This work constructed an effective photosensitizer for diagnosing and treating cancers and evaluating PDT efficacy.