State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
University of Science and Technology of China, Hefei, 230026, China.
Adv Mater. 2021 Sep;33(36):e2101467. doi: 10.1002/adma.202101467. Epub 2021 Jul 23.
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 ) 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 sonosensitizer, the GSH-Pt-VS 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.
提高肿瘤内活性氧（ROS）的声敏剂的开发和优化在当前的声动力学治疗（SDT）中确实很有吸引力。有鉴于此，与最广泛探索的声敏剂相比，具有更窄带隙的支化四硫化钒（VS）纳米树枝状结构被提出作为一种新的声敏剂来源，它允许更轻松地分离超声触发的电子-空穴对以产生 ROS。具体来说，铂（Pt）纳米粒子和内源性高浓度谷胱甘肽（GSH）被合理设计，以进一步优化其声敏化性能。作为共催化剂，Pt 有利于捕获电子，而 GSH 作为天然空穴清除剂，倾向于捕获空穴。与原始 VS 声敏剂相比，GSH-Pt-VS 纳米复合材料可以大大延长电荷的寿命，并赋予其高效的 ROS 产生活性。此外，这些纳米平台能够重塑肿瘤微环境以实现 ROS 的过度产生，这得益于克服肿瘤缺氧以提高 SDT 触发的单线态氧产生，催化内源性过氧化氢转化为破坏性羟基自由基进行化学动力学治疗，以及耗尽 GSH 以放大肿瘤内氧化应激。所有这些综合效应导致显著有效的肿瘤抑制效果。本研究丰富了声敏剂研究，并证明声敏剂可以通过电荷分离工程策略进行合理优化。
