Using the Electronic Grab-Transport Mechanism to Construct Metal–Organic Frameworks with Type I/II Dual Sonodynamic Therapy Reinforcement

Sonodynamic therapy (SDT) has demonstrated promising potential in the treatment of tumors and has attracted widespread attention. The majority of sound-sensitive materials developed to date have been categorized as oxygen-dependent type II sonosensitizers (SSs), which are susceptible to tumor hypoxia and significantly limit their efficacy. In this study, highly active porphyrin-based metal-organic frameworks (Yb-TCPP PMOF) with type I/II SDT dual actions were constructed by regulating the electron transfer process between metal nodes and ligands, which can produce multiple reactive oxygen species (ROS) such as ¹O₂, O₂^•-, and •OH. After that, the energy level barrier of triplet SSs was reduced by in situ loading of Au nanoparticles with the electronic grab-transport (EGT) effect, and the ROS yield was increased by accelerating the electron transport. Intriguingly, the successful construction of Au/Yb-TCPP not only produced abundant oxygen vacancy defects but also reduced the band gap, which effectively facilitated the electron-hole separation of SSs and further improved the SDT efficiency by inhibiting its recombination process. Furthermore, we also found that these ultrasmall Au nanoparticles in the MOF structure can act as catalase and undergo cascade reactions with glucose oxidase and obtain a self-producing oxygen circulation system (Au/Yb-TCPP@GOx) by reducing glucose through the coordination of nanoenzyme and bioenzyme. This not only significantly alleviates the hypoxia state of tumors but also has a starvation effect on tumor cells. Finally, it was verified at the levels of tumor cells and mice that Au/Yb-TCPP@GOx can effectively inhibit tumors through the dual effects of enhanced type I and type II SDT, as well as the starvation effect. The composite materials constructed showed a multisynergistic enhancement effect, which has guiding significance for improving electron transport, alleviating tumor hypoxia, enhancing ROS yield, and constructing starvation treatment strategies.