Dual-organelle targeted photosensitizer with AIE characteristics for triple-negative breast cancer photodynamic therapy via apoptosis and immunogenic cell death

Triple-negative breast cancer (TNBC) is a highly malignant breast cancer with a high metastasis rate, weak targeted therapy effect, and short patient survival period. Current treatments have significant limitations, highlighting an urgent need for novel therapies to alleviate patient suffering. Photodynamic therapy (PDT) has emerged as a promising antitumor strategy by inducing apoptosis and immune responses through the release of reactive oxygen species (ROS). However, conventional photosensitizers (PSs) face issues such as high cytotoxicity and aggregation-caused quenching (ACQ), limiting their clinical applicability. To address these challenges, we developed a novel dual-targeting, bimolecular pathway using an advanced photosensitizer, 2TPA-PIMe, designed based on aggregation-induced emission (AIE). The rationally designed 2TPA-PIMe, incorporating alkylated phosphindole as the core, exhibits AIE properties and efficient ROS generation via both type I and type II pathways, potentially enhancing PDT effectiveness in vivo. This approach achieves an effective dual-targeting, dual-mechanism pathway, offering new directions and methodologies for treating TNBC.