Metal–Organic Frameworks Based on Fluorogens with Aggregation-Induced Emission for Enhanced Sonodynamic Therapy

Sonodynamic therapy (SDT) with largely improved penetration depth over photodynamic therapy has shown promising performance in noninvasive tumor treatment but is limited by insufficient reactive oxygen species (ROS). We report a metal–organic framework (MOF) constructed from fluorgens with aggregation-induced emission (AIEgens) that possesses the unique aggregation-enhanced ROS generation ability for SDT. The SDT’s effect of this TPPE-Zn-MOF is enhanced for the following reasons. First, TPPE is coordinated by Zn cluster which restricts its intramolecular motions, and hence florescence and intersystem cross (ISC) processes are promoted; second, the presence of Zn centers increases the spin orbital coupling and further promotes the ISC process; Last but not least, the porous structure and large specific surface area (620.97 m2/g) of TPPE-Zn-MOF further enhance the cavitation effect and oxygen loading for efficient ROS generation, which also promote the fast diffusion of short-lived ROS into the surrounding microenvironment. The designed TPPE-Zn-MOF thus could generate more efficiently singlet oxygen (type II ROS) and superoxide anion radical (type I ROS) than TPPE ligand, which is also superior over commercial sonosensitizers methylene blue and rose bengal. Both in vitro and in vivo experiments further prove the excellent SDT antitumor effect of the TPPE-Zn-MOF. The AIEgen-based MOF simultaneously promotes the generation of triplet-state excitons and the interaction between oxygen and cavitation bubbles, which demonstrates a new approach for sonosensitizer design for SDT-related treatments.