MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
ACS Appl Mater Interfaces. 2020 Jul 15;12(28):31205-31216. doi: 10.1021/acsami.0c07886. Epub 2020 Jul 6.
Oxidative stress induced by reactive oxygen species (ROS) is one of the major pathological mechanisms of acute kidney injury (AKI). Inorganic nanomaterial-mediated antioxidant therapy is considered a promising method for the prevention of AKI; however, currently available antioxidants for AKI exhibit limited clinical efficacy due to the glomerular filtration threshold (∼6 nm). To address this issue, we developed ultrasmall RuO nanoparticles (RuONPs) (average size ≈ 2 nm). The NPs show excellent antioxidant activity and low biological toxicity. In addition, they can pass through the glomerulus to be excreted. These properties in combination make the ultrasmall RuONPs promising as a nanozyme for the prevention of AKI. The NP catalytic properties mimic the activity of catalase, peroxidase, superoxide dismutase, and glutathione peroxidase. The nanozyme can be efficiently and rapidly absorbed by human embryonic kidney cells while significantly reducing ROS-induced apoptosis by eliminating excess ROS. After intravenous injection, the ultrasmall RuONPs significantly inhibit the development of AKI in mice. In vivo toxicity experiments demonstrate the biosafety of the NPs after long-term preventing. The multienzyme-like activity and biocompatibility of the ultrasmall RuONPs makes them of great interest for applications in the fields of biomedicine and biocatalysis.
活性氧（ROS）引起的氧化应激是急性肾损伤（AKI）的主要病理机制之一。无机纳米材料介导的抗氧化治疗被认为是预防 AKI 的一种有前途的方法；然而，目前用于 AKI 的抗氧化剂由于肾小球滤过阈值（~6nm）而表现出有限的临床疗效。为了解决这个问题，我们开发了超小的 RuO 纳米颗粒（RuONPs）（平均尺寸≈2nm）。这些 NPs 表现出优异的抗氧化活性和低生物毒性。此外，它们可以通过肾小球滤过并被排出。这些特性结合在一起，使得超小的 RuONPs 有望成为预防 AKI 的纳米酶。NP 的催化特性模拟了过氧化氢酶、过氧化物酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。纳米酶可以高效快速地被人胚肾细胞吸收，同时通过消除过量的 ROS 显著减少 ROS 诱导的细胞凋亡。静脉注射后，超小的 RuONPs 显著抑制了小鼠 AKI 的发展。体内毒性实验证明了 NPs 在长期预防后的生物安全性。超小的 RuONPs 的多酶样活性和生物相容性使它们在生物医学和生物催化领域的应用具有很大的吸引力。
