Ag-Doped Metal-Organic Frameworks Heterostructure for Sonodynamic Therapy of Deep-Seated Cancer and Bacterial Infection '

Metal-organic frameworks (MOF) have attracted great potential in sonodynamic therapy (SDT) owing to large sonosensitizers' loading and fast reactive oxygen species' (ROS) diffusion; however, the low ligand-to-metal charge transfer efficiency sharply impairs the SDT effect. Herein, we report the design of MIL@Ag heterostructures with high electron-hole pairs separation efficiency and enhanced diverse ROS generation ability for deep-seated cancer treatment and bacterial infection. The MIL@Ag heterostructure is composed of Ti-based MOFs (named MIL), on which are in situ assembled silver nanoparticles (Ag NPs). The electrochemical experiments and density functional theory calculations verify that the introduction of Ag NPs can significantly improve the electron transfer efficiency and O2 adsorption capacity of MIL. Under ultrasound irradiation, the doped Ag NPs can trap the activated electrons from MIL to reduce surrounding O2 and produce superoxide radicals (center dot O2-), while the activated holes enable oxidizing H2O to produce hydroxyl radicals (center dot OH). Thus, they efficiently improve the therapeutic efficiency of SDT. MIL@Ag-PEG-mediated SDT implements A549 cancer cells' killing under a tissue barrier of 2 cm and eradicates the bacterial infection of Staphylococcus aureus, thus promoting wound healing. Therefore, MIL@Ag-PEG provides a promising strategy for augmenting SDT performance by rational heterostructure design of sonosensitizers.