Three‐Pronged Attack by Homologous Far‐red/NIR AIEgens to Achieve 1+1+1>3 Synergistic Enhanced Photodynamic Therapy
Wenhan Xu, Michelle M. S. Lee, Jing‐Jun Nie, Zhihan Zhang, Ryan T. K. Kwok, Jacky W. Y. Lam, Fu‐Jian Xu, Dong Wang, Ben Zhong Tang
Abstract
Abstract Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation‐induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far‐red/near‐infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three‐pronged PDT.