Wang Li, Zhang Baorui, Yang Xueting, Guo Shuaitian, Waterhouse Geoffrey I N, Song Guangrong, Guan Shanyue, Liu Aihua, Cheng Liang, Zhou Shuyun
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Bioact Mater. 2022 May 25;20:126-136. doi: 10.1016/j.bioactmat.2022.05.012. eCollection 2023 Feb.
In acute ischemic stroke therapy, potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species (ROS) during ischemic reperfusion. Herein, a novel 2D neuroprotective agent (AFGd-LDH) is reported, comprising Gd-containing layered double hydroxide nanosheets (Gd-LDH, as a drug nanocarrier/MRI contrast agent), atorvastatin (ATO, as a neuroprotective drug) and the ferritin heavy subunit (FTH, as a blood brain barrier transport agent). Experiments revealed AFGd-LDH to possess outstanding antioxidant activity, neuroprotective properties, blood‒brain barrier transit properties, and biocompatibility. studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be ∼90%, surpassing CeO (50%, a ROS scavenger) and edaravone (52%, a clinical neuroprotective drug). Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion, reducing the infarct area by 67% and lowering the neurological deficit score from 3.2 to 0.9. AFGd-LDH also offered outstanding MRI performance, thus enabling simultaneous imaging and ischemia reperfusion therapy.
在急性缺血性中风治疗中,需要强效神经保护剂来预防缺血再灌注期间由活性氧(ROS)引起的神经损伤。在此,报道了一种新型二维神经保护剂(AFGd-LDH),它由含钆层状双氢氧化物纳米片(Gd-LDH,作为药物纳米载体/磁共振成像造影剂)、阿托伐他汀(ATO,作为神经保护药物)和铁蛋白重链亚基(FTH,作为血脑屏障转运剂)组成。实验表明AFGd-LDH具有出色的抗氧化活性、神经保护特性、血脑屏障通透特性和生物相容性。研究证明AFGd-LDH的ROS清除效率约为90%,超过了CeO(50%,一种ROS清除剂)和依达拉奉(52%,一种临床神经保护药物)。对小鼠缺血再灌注模型的研究表明,AFGd-LDH可显著减少再灌注诱导的细胞凋亡,使梗死面积减少67%,并将神经功能缺损评分从3.2降至0.9。AFGd-LDH还具有出色的磁共振成像性能,从而能够同时进行成像和缺血再灌注治疗。