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用于急性肾损伤治疗的活性氧和游离DNA清除MnO纳米酶

Reactive Oxygen Species- and Cell-Free DNA-Scavenging MnO Nanozymes for Acute Kidney Injury Therapy.

作者信息

Meng Longxiyu, Feng Jiayuan, Gao Jie, Zhang Yihong, Mo Wenjing, Zhao Xiaozhi, Wei Hui, Guo Hongqian

机构信息

Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology Nanjing University, Nanjing, Jiangsu 210008, China.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu 210093, China.

出版信息

ACS Appl Mater Interfaces. 2022 Nov 16;14(45):50649-50663. doi: 10.1021/acsami.2c16305. Epub 2022 Nov 5.

DOI:10.1021/acsami.2c16305
PMID:36334088
Abstract

Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, MnO nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, MnO Nfs could protect HK2 cells through cascade ROS scavenging (dismutating O into HO by superoxide dismutase-like activity and then decomposing HO by catalase-like activity). Second, MnO Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia-reperfusion AKI murine models. Furthermore, MnO Nfs could be used for the -MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.

摘要

针对急性肾损伤(AKI)的活性氧(ROS)清除疗法前景广阔,但尚未开发出有效的ROS清除药物。此外,游离细胞DNA(cfDNA)也与AKI有关,但相应的治疗方法尚未得到充分发展。为应对这些挑战,开发了具有ROS和cfDNA清除活性的MnO纳米花(Nfs),以更好地保护AKI,具体如下。首先,MnO Nfs可通过级联ROS清除(通过类似超氧化物歧化酶的活性将O歧化为HO,然后通过类似过氧化氢酶的活性分解HO)来保护HK2细胞。其次,MnO Nfs可有效吸附cfDNA,然后减少由cfDNA引起的炎症。综合起来,在顺铂诱导的和缺血再灌注AKI小鼠模型中均取得了显著的治疗效果。此外,MnO Nfs可用于AKI的磁共振成像(MRI)实时成像。这项研究不仅为AKI提供了一种有前景的治疗方法,还展示了纳米酶的转化潜力。

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