Aggregation-induced emission near-infrared photosensitizer with time-responsive dual-organelles targeting for accelerating cancer cells apoptosis and metastasis inhibition

Abstract

Photodynamic therapy (PDT) combined with critical organelle targeting can maximize ablation of malignant tumors, which is a desirable route against cancer. However, the short excitation/emission wavelengths of conventional photosensitizers (PSs), the inefficient production of reactive oxygen species (ROS) and the inevitable aggregation-induced quenching phenomenon have restricted their development. Herein, we developed and synthesized a set of photoactivated fluorescent probes named MoTQu and MeTQu with aggregation-induced emission properties. The both of fluorescent probes have merits of bright near-infrared fluorescence emission, large stokes shift and enhanced intramolecular charge transfer attributed to the synergistic interaction of strong donor and acceptor of molecular. In addition, the optimal PS named MoTQu not only possesses superior anti-photobleaching, biocompatibility and extremely high-level ROS generation efficiency, on the other hand, can time-responsive target mitochondria and lysosomes in living cells to cause lysosomal dysfunction by generating large amount of ROS in situ under photoexcitation, subsequently targeting mitochondria through the positive electrical properties of the quinoline fraction, further inducing and promoting cancer cell damage and irreversible apoptosis. Consequently, we are convinced that MoTQu can be a powerful tool to foster the development of image-guided PDT.