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The development of targeted therapies for CI\u2010AKI may improve the efficacy of chemotherapy while mitigating renal toxicity. Given that ferroptosis is a key pathological mechanism in CI\u2010AKI, targeted drug delivery systems against this process represent a promising therapeutic strategy. Dipeptidase 1 (DPEP1) is highly expressed in renal proximal tubular brush borders and has been associated with ferroptosis regulation and tubular injury. In this study, mesoporous polydopamine nanoparticles (MPDA NPs) were engineered for renal\u2010targeted delivery of cilastatin sodium (CTT), a specific DPEP1 inhibitor, through L\u2010serine (L\u2010Ser) surface modification (CTT\/MPDA@L\u2010Ser NPs). In vitro experiments demonstrated that CTT\/MPDA@L\u2010Ser NPs inhibited the expression of DPEP1 to upregulate the expression of the ferroptosis\u2010suppressing protein glutathione peroxidase 4 (GPX4), thereby suppressing ferroptosis pathways. In AKI mice, CTT\/MPDA@L\u2010Ser NPs exhibited selective renal accumulation, significantly ameliorating serum creatinine and blood urea nitrogen levels.\u00a0Collectively, CTT\/MPDA@L\u2010Ser NPs exhibited potent therapeutic efficacy against AKI, presenting a promising strategy for targeted AKI management.<\/jats:p>","DOI":"10.1002\/advs.77090","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:46:55Z","timestamp":1786636015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kidney\u2010Targeted Cilastatin Nanoparticles Inhibit DPEP1\u2010Mediated Ferroptosis for Acute Kidney Injury Therapy"],"prefix":"10.1002","author":[{"given":"Wanbing","family":"Qin","sequence":"first","affiliation":[{"name":"Jieyang Medical Research Center Jieyang People's Hospital  Jieyang Guangdong 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