AIEgen-Based Dual-Functional Platform for Cancer Cell Imaging and Photodynamic Therapy

Abstract A new paradigm shift in translational healthcare research focuses on the development of a minimally invasive image-guided therapeutic strategy. The current study presents the design and synthesis of a series of donor–acceptor (D–A)-type aggregation-induced emission luminogens (AIEgens) specifically engineered for room temperature phosphorescence (RTP) emission and efficient photodynamic therapy. The newly synthesized AIEgen molecules incorporate an electron-rich thianthrene unit and a strong electron-withdrawing malononitrile moiety, forming a highly conjugated D–A system that promotes intramolecular charge transfer (ICT). The presence of bromine enhances spin–orbit coupling (SOC), enabling RTP emission and efficient intracellular reactive oxygen species (ROS) generation. The synthesized AIEgens exhibited strong emission in the aggregated state, which, upon light irradiation, generated elevated ROS levels, resulting in a significant dose-dependent reduction in cell viability. Among the three AIEgens evaluated, 2-BrTM showed the highest mitochondrial membrane depolarization of 48% and 30.1% upon light irradiation, compared to 7.57% and 3.43% in the dark condition for the breast cancer MCF-7 and MDA-MB-231 cells, respectively, demonstrating a pronounced photodynamic effect. Flow cytometric analysis confirmed that 2-BrTM induced early apoptosis, contributing to photoinduced cytotoxicity. The synthesized AIEgens exhibited efficient RTP with high quantum yields, yielding bright, long-lived emission suitable for bioimaging and cancer theranostics. In vivo mice studies further substantiated excellent biocompatibility of the compounds. Notably, this work demonstrated the potential of AIEgen-based RTP materials platforms for photodynamic therapy via ROS-mediated mitochondrial dysfunction and apoptosis.