Low-side-effect phototherapy using aggregation-induced emission agents with “turn-on” and “turn-off” strategies

Photodynamic therapy (PDT) is a leading approach in modern oncology due to its ability to selectively eliminate cancer cells. The hydrophilic nature of traditional photosensitizers (PSs) often leads to aggregation in the biological environment reducing treatment efficiency. The PSs with aggregation-induced emission (AIE) characteristics ensure PSs retain or even enhance their efficacy in aggregated states. However, the non-specific accumulation of AIE PSs in healthy cells, especially in those near tumors, as well as the residual presence of AIE PSs after PDT treatment, presents notable challenges to the safety of PDT. To enhance the safety of PDT impacted by these two factors, researchers have developed activatable turn-on AIE PSs by cancer-specific biomarkers, as well as degradable turn-off AIE PSs. This review summarizes the recent advancements in cancer biomarkers-activated turn-on AIE PSs and degradable turn-off AIE PSs. The strategies of turn-on AIE PSs are mainly based on the mechanisms of photoinduced electron transfer (PET), Förster resonance energy transfer (FRET), intersystem crossing, and enhancing the accessibility of oxygen that controls their activation. The strategies of turn-off AIE PSs are based on self-degradation and endogenous ROS degradation, respectively.