School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
School of Life Sciences, Shanghai University, Shanghai 200444, China.
ACS Appl Mater Interfaces. 2021 Sep 29;13(38):45325-45334. doi: 10.1021/acsami.1c14701. Epub 2021 Sep 17.
Sonosensitizers play crucial roles in the controlled production of reactive oxygen species (ROS) under ultrasound (US) irradiation with high tissue-penetration depth for noninvasive solid tumor therapy. It is desirable to fabricate structurally simple yet multifunctional sonosensitizers from ultrafine nanoparticles for ROS-based multimode therapy to overcome monomode limitations such as low ROS production yields and endogenous reductive glutathione (GSH) to ROS-based treatment resistance. We report the facile high-temperature solution synthesis of ultrafine W-doped TiO (W-TiO) nanorods for exploration of their sonodynamic, chemodynamic, and GSH-depleting activities in sonodynamic-chemodynamic combination tumor therapy. We found that W and W ions doped in W-TiO nanorods play multiple roles in enhancing their ROS production. First, W doping narrows the band gap from 3.2 to 2.3 eV and introduces oxygen and Ti vacancies for enhancing their sonodynamic performance. Second, W doping endows W-TiO nanorods with Fenton-like reaction activity to produce •OH from endogenous HO in the tumor. Third, W ions reduce endogenous GSH to glutathione disulfide (GSSG) and, in turn, form W ions that further enhance their chemodynamic activity, which greatly modifies thae oxidation-reduction tumor microenvironment in the tumor. In vivo experiments display the excellent ability of W-TiO nanorods for enhanced tumor eradication in human osteosarcoma models under single US irradiation. Importantly, the ultrafine nanorod morphology facilitates rapid excretion from the body, displaying no significant systemic toxicity. Our work suggests that multivalent metal doping in ultrafine nanomaterials is an effective and simple strategy for the introduction of new functions for ROS-based multimode therapy.
声敏剂在超声（US）辐照下控制活性氧（ROS）的产生中起着至关重要的作用，具有较高的组织穿透深度，可用于无创性实体肿瘤治疗。从超细纳米颗粒中制造结构简单但多功能的声敏剂，用于基于 ROS 的多模式治疗，以克服单模式的局限性，如低 ROS 产生产率和内源性还原型谷胱甘肽（GSH）对基于 ROS 的治疗的抗性，这是很理想的。我们报告了一种简便的高温溶液合成超细 W 掺杂 TiO（W-TiO）纳米棒的方法，用于探索其在声动力-化学动力学联合肿瘤治疗中的声动力、化学动力学和 GSH 耗竭活性。我们发现，W 和 W 离子掺杂在 W-TiO 纳米棒中在增强其 ROS 产生方面发挥了多种作用。首先，W 掺杂将带隙从 3.2 eV 缩小到 2.3 eV，并引入氧和 Ti 空位以增强其声动力性能。其次，W 掺杂赋予 W-TiO 纳米棒类 Fenton 反应活性，可从肿瘤内的内源性 HO 产生 •OH。第三，W 离子将内源性 GSH 还原为谷胱甘肽二硫化物（GSSG），并进一步形成 W 离子，从而增强其化学动力学活性，这极大地改变了肿瘤中的氧化还原肿瘤微环境。体内实验显示，在单超声照射下，W-TiO 纳米棒在人骨肉瘤模型中具有增强肿瘤消除的优异能力。重要的是，超细纳米棒形态有利于从体内快速排泄，没有明显的全身毒性。我们的工作表明，多价金属掺杂在超细纳米材料中是一种引入基于 ROS 的多模式治疗新功能的有效且简单的策略。
