A high performance AIE-active sonosensitizer for efficient sonodynamic tumor therapy

Ultrasound-triggered sonodynamic therapy (SDT) presents growing promise in deep-seated or unresectable tumor inhibition because of the perfect tissue penetration ability. However, its therapeutic efficacy is always restricted by the limited reactive oxygen species (ROS) generation ability of sonosensitizers. In this work, based on molecular engineering, we have fabricated aggregation-induced emission (AIE)-active organic sonosensitizers bearing efficient ROS generation with US irradiation for tumor treatment. By enhancing the intramolecular charge transfer strength and intermolecular interaction, an organic sonosensitizer with reduced energy gap and AIE features was developed, presenting enhanced oxygen sensitization behavior to produce ROS upon an ultrasound trigger compared to Ce 6. Moreover, the excellent mitochondrial enrichment of the obtained sonosensitizer enables effective tumor cell eradication via apoptotic and ferroptosis pathways with ultrasound irradiation. The efficient in vivo tumor inhibition was also achieved based on the SDT approach. Therefore, this work provided a generalized and promising strategy for deep-seated or unresectable tumor treatment in the clinic.