A Robust Narrow Bandgap Vanadium Tetrasulfide Sonosensitizer Optimized by Charge Separation Engineering for Enhanced Sonodynamic Cancer Therapy

Abstract The development and optimization of sonosensitizers for elevating intratumoral reactive oxygen species (ROS) are definitely appealing in current sonodynamic therapy (SDT). Given this, branched vanadium tetrasulfide (VS 4 ) nanodendrites with a narrower bandgap (compared with the most extensively explored sonosensitizers) are presented as a new source of sonosensitizer, which allows a more effortless separation of sono‐triggered electron–hole pairs for ROS generation. Specifically, platinum (Pt) nanoparticles and endogenous high levels of glutathione (GSH) are rationally engineered to further optimize its sono‐sensitized performance. As cocatalyst, Pt is conducive to trapping electrons, whereas GSH, as a natural hole‐scavenger, tends to capture holes. Compared with the pristine VS 4 sonosensitizer, the GSH‐Pt‐VS 4 nanocomposite can greatly prolong the lifetime of the charge and confer a highly efficacious ROS production activity. Furthermore, such nanoplatforms are capable of reshaping tumor microenvironments to realize ROS overproduction, contributed by overcoming tumor hypoxia to improve SDT‐triggered singlet oxygen production, catalyzing endogenic hydrogen peroxide into destructive hydroxyl radicals for chemodynamic therapy, and depleting GSH to amplify intratumoral oxidative stress. All these combined effects result in a significantly efficient tumor suppression outcome. This study enriches sonosensitizer research and proves that sonosensitizers can be rationally optimized by charge separation engineering strategy.