He Shan, Chen Chaoran, Li Fangzheng, Xu Wenxuan, Li Dongdong, Liang Ming, Yang Xianzhu
School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, P. R. China.
Nano Lett. 2023 Oct 11;23(19):8978-8987. doi: 10.1021/acs.nanolett.3c02531. Epub 2023 Sep 19.
Acute kidney injury (AKI) is closely associated with the overproduction of reactive oxygen species (ROS), which can cause multiple organ dysfunctions without timely treatment. However, only supportive treatments are currently available for AKI in clinics. Here, we developed nanomaterials of hyperbranched polyphosphoester (PPE) containing abundant thioether (S-PPE NP) and thioketal bonds (TK-PPE NP). Our data demonstrates that S-PPE NP exhibits an excellent capability of absorbing and scavenging multiple types of ROS, including HO, •OH, and •O, via thioether oxidation to sulfone or sulfoxide; it was also determined that S-PPE NP efficiently eliminates intracellular ROS, thus preventing cellular damage. Moreover, S-PPE NP was able to efficiently accumulate in the injured kidneys of AKI-bearing mice. As a result, the administration of S-PPE NP provided a superior therapeutic effect in AKI-bearing mice by downregulating ROS- and inflammation-related signaling pathways, thus reducing cell apoptosis. This thioether-containing polymer represents a promising broad-spectrum ROS scavenger that can be used for effective AKI treatments.
急性肾损伤（AKI）与活性氧（ROS）的过度产生密切相关，若不及时治疗，ROS可导致多器官功能障碍。然而，目前临床上对AKI仅有支持性治疗方法。在此，我们制备了含有丰富硫醚（S-PPE NP）和硫酮键（TK-PPE NP）的超支化聚磷酸酯（PPE）纳米材料。我们的数据表明，S-PPE NP通过硫醚氧化为砜或亚砜，展现出优异的吸收和清除多种类型ROS的能力，包括HO、•OH和•O；还确定S-PPE NP能有效消除细胞内ROS，从而防止细胞损伤。此外，S-PPE NP能够在AKI小鼠的受损肾脏中有效蓄积。结果，给予S-PPE NP通过下调ROS和炎症相关信号通路，在AKI小鼠中提供了卓越的治疗效果，从而减少细胞凋亡。这种含硫醚聚合物代表了一种有前景的广谱ROS清除剂，可用于有效的AKI治疗。
