文献类型：期刊文献

英文题名：A Ferroptosis-Inhibitive Polypeptosome for Synergistic Management of Acute Kidney Injury Through Antioxidation and Iron Binding

作者：Liu, Danqing[1,2];Zhang, Wenqing[3];Fan, Zhen[2,3];He, Shisheng[1];Du, Jianzhong[1,2,3,4]

机构：[1]Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Orthoped, Shanghai 200072, Peoples R China;[2]Tongji Univ, Shanghai Peoples Hosp 4,Shanghai key Lab Anesthes, Dept Gynaecol & Obstetr,Sch Med, Clin ResearchCenter Anesthesiol & Perioperat Med, Shanghai 200434, Peoples R China;[3]Tongji Univ, Sch Mat Sci & Engn, Dept Polymer Mat, 4800 Caoan Rd, Shanghai 201804, Peoples R China;[4]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：34

期号：51

外文期刊名：ADVANCED FUNCTIONAL MATERIALS

收录：;EI(收录号：20243316865168);WOS:【SCI-EXPANDED(收录号:WOS:001288211600001)】；

基金：This research was supported by the National Natural Science Foundation Of China (21925505, 22335005, 22075212, 22305176), National Key R&D Program of China (2022YFC2402900), Innovation Program of Shanghai Municipal Education Commission (2023ZKZD28) and the China Postdoctoral Science Foundation (2024T170667 and 2023M732630). J.D. is the recipient of a 5-year National Science Fund for Distinguished Young Scholars.

语种：英文

外文关键词：antioxidation; ferroptosis; iron binding; polymersomes; self-assembly

摘要：Acute kidney injury (AKI) is a critical condition with a wide range of triggers that cause heavy burden on public health. Despite its high incidence and mortality, the treatment of AKI still highly relies on hemodialysis, which is costly and usually accompanied by severe complications. Therefore, development of new therapeutic targets and methods for AKI is urgently needed. Herein, a ferroptosis-targeting strategy for AKI treatment by rationally designed ferroptosis-inhibitive polypeptide-based polymersomes (polypeptosomes, FIPs) is proposed. Such FIPs are self-assembled from poly(glutamic acid)-block-poly(methionine-stat-tyrosine) [PGA(9)-b-P(Met(8)-stat-PTyr(13))]. The ferroptosis-inhibition function of the FIPs arises from the rationally-selected amino acid composition: P(Met-stat-Tyr) endows the FIPs with a high scavenging efficiency of over 90% toward different reactive oxygen species (ROS); while the glutamate and tyrosine residues, as well as the amide groups, can bind iron ions, thus blocking iron overload and lipid peroxide in cells. In vivo experiments confirm that the FIPs can effectively alleviate oxidative stress, inhibit ferroptosis, and restore kidney functions. Transcriptome sequencing further reveals the therapeutic mechanisms of FIPs. Overall, such polypeptosomes capable of blocking multiple pathways of ferroptosis open a new avenue for AKI treatment and provide fresh insights into the development of generalized therapies for inflammation.