Acceptor Elongation Boosted Intersystem Crossing Affords Efficient NIR Type-I and AIE-Active Photosensitizers for Targeting Ferroptosis-Based Cancer Therapy

Abstract

Photosensitizers (PSs) featuring type I reactive oxygen species (ROS) generation and aggregation-induced emission (AIE) activity offer a promising solution to achieve non-invasive and precise theranostics. However, the reported AIE luminogens (AIEgens) with both AIE characteristic and strong type-I ROS generation are still scarce and the structure-property relationship is still unclear. Herein, an innovative acceptor elongation boosted intersystem crossing (AEBIC) design strategy has been proposed to endow the AIEgen strong type-I ROS producibility. The results indicate that the obtained AIEgen exhibit type-I ROS and aggregation-enhanced ROS efficacy, which has been verified by both experimental and theoretical results. Mechanistic study reveal that the acceptor elongation has promoted a dual-channel intersystem crossing pathway to enhance the intersystem crossing (ISC) process due to the differences in triplet configurations, which can be further amplified by aggregation. The afforded type-I AIE-PS show lipid droplet-anchored characteristic and can induce the ferroptosis through destroying the cellular redox homeostasis and increasing lethal levels of lipid peroxidation. Finally, targeting ferroptosis-based cancer therapy can be realized with excellent anti-tumor effect.