Preparation and mechanism of heterogeneous MX@MIL-125(Ti) towards sonodynamic therapy

Sonodynamic therapy (SDT), as a burgeoning non-invasive treatment technology, can utilize ultrasound (US) irradiation to excite sonosensitizers for generating reactive oxygen species (ROS), thereby achieving to kill deep-seated tumors. However, the development of sonosensitizers with high sonosensitivity and good biocompatibility remains a large challenge. Herein, a novel titanium-based metal-organic frameworks (Ti-MOFs) was successfully fabricated by introducing Ti₃C₂ MXene to replace the traditional titanium (Ti) source of MIL-125(Ti), and served as a heterogeneous sonosensitizer to construct high-efficiency SDT platform. Through structural design and surface modification, the obtained MX@MIL-125(Ti) was optimized to have a size of approximately 112 nm, and its sonosensitive performance and biocompatibility was also enhanced significantly. Both in vitro and in vivo experiments confirmed that such MX@MIL-125(Ti) exhibited superior ROS generation capability under US irradiation compared to traditional MIL-125(Ti), and could achieve high-efficiency anti-tumor activity, with a tumor inhibition rate exceeding 80%. In addition, the excellent biocompatibility of MX@MIL-125(Ti) provided significant support for clinical translation. In a word, this study seeks some breakthroughs for the development of high-sensitivity good-biocompatibility sonosensitizers, and will promote the practical application of SDT in tumor treatment.