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Oxidative stress, coupled with excessive inflammation, is the main pathological mechanism for AKI. Specifically, complement component 5a (C5a) exacerbates the vicious cycle between oxidative stress and inflammatory responses. Herein, we developed a cascade\u2010functioning mirror\u2010image DNA nanostructure, L\u2010DNA tetrahedron (LDT), for sequentially blocking the extracellular complement C5a to alleviate inflammation and eliminating intracellular reactive oxygen species (ROS) to inhibit oxidative stress. A C5a\u2010neutralizing mirror\u2010image aptamer (LA) was incorporated into LDT via a ROS\u2010sensitive linker (thioketal, i.e., TK bond), which enabled the release of LA in the inflammatory microenvironment to block C5a. LA\u2010conjugated LDT (LDT\u2010LA) exhibited preferential renal uptake and enhanced renal retention compared with its counterpart made of D\u2010nucleic acids and provided effective treatment in ischemia\u2010reperfusion (I\/R)\u2010, cisplatin\u2010, and glycerol\u2010induced AKI mouse models. Meanwhile, LDT\u2010LA exhibits excellent biocompatibility, making it a promising candidate for AKI therapy. The biostable, cascade\u2010functioning LDT\u2010LA could act as a multifunctional platform for the treatment of other diseases by conjugating with appropriate functional groups.<\/jats:p>","DOI":"10.1002\/anie.4575346","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:30:23Z","timestamp":1788258623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co\u2010Assembled Mirror\u2010Image DNA Nanostructure for Effective Alleviation of Acute Kidney Injury"],"prefix":"10.1002","volume":"65","author":[{"given":"Yiming","family":"Xie","sequence":"first","affiliation":[{"name":"Laboratory of Nanosystem and Hierarchical Fabrication National Center for Nanoscience and Technology  Beijing China"},{"name":"School of Materials Science and Engineering Zhengzhou University  Zhengzhou 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