All-in-One Molecular Aggregation-Induced Emission Theranostics: Fluorescence Image Guided and Mitochondria Targeted Chemo- and Photodynamic Cancer Cell Ablation

Molecular theranostic platforms with precise molecular structure and multiple functions hold great promise for cancer therapy. Different from the current strategy to incorporate various components into single entities with the risk of compromised efficacy and poor reproducibility, herein, molecular aggregation-induced emission (AIE) photosensitizers with ingenious integration of AIE fluorophore and cisplatin are facilely synthesized for synergetic anticancer therapy. Through adjusting donor structures coordinated with a cisplatin moiety and balancing the hydrophobic–hydrophilic property, donor–acceptor strength, and intramolecular charge transfer effect, the newly designed AIE photosensitizer TNPT exhibits good cellular uptake with predominant mitochondria location of cancerous cells, high chemotherapeutic efficacy similar to that of cisplatin, and strong reactive oxygen species (ROS) generation capability better than that of chlorin e6 (Ce6). Importantly, TNPT demonstrates synergetic photodynamic and chemotherapy on C6 glioma cells, showing 2.4-fold more potency than cisplatin upon white light irradiation (15 J/cm2). Further cell cycle analysis and apoptosis assay indicate that the photodynamic and chemo-therapeutic functions of TNPT synergistically inhibit DNA replication and cause cell apoptosis. In addition, TNPT exhibits selective uptake on cancerous cells rather than normal cells, contributing to significantly lower cytotoxicity to normal cells as compared to free cisplatin. This study provides a facile strategy to design molecular theranostic agents.