{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:50:17Z","timestamp":1793022617741,"version":"4.5.0"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","award":["2025-BS-0754"],"award-info":[{"award-number":["2025-BS-0754"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M773577"],"award-info":[{"award-number":["2025M773577"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007620","name":"Department of Education of Liaoning Province","doi-asserted-by":"publisher","award":["LJ212510163010"],"award-info":[{"award-number":["LJ212510163010"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273878"],"award-info":[{"award-number":["82273878"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473872"],"award-info":[{"award-number":["82473872"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI) is a life-threatening syndrome in which oxidative stress, ferroptosis, and inflammatory amplification converge to damage renal proximal tubular epithelial cells. Although antioxidant and antiferroptotic therapies are conceptually attractive, their efficacy is restricted by rapid clearance and insufficient accumulation in injured renal tubules. Here, we report lysozyme-associated quercetin\u2013manganese metal\u2013phenolic nanocomposites (QMLNCs) as a kidney-targeted therapeutic platform for AKI. In this design, quercetin (QCT) functions simultaneously as an antioxidant drug and a phenolic coordination ligand, while Mn2+ participates in metal\u2013phenolic network formation. Lysozyme is incorporated through noncovalent protein\u2013polyphenol interactions to enhance megalin-mediated uptake by proximal tubular cells. QMLNCs exhibited favorable colloidal stability, H2O2-responsive release, and broad-spectrum radical-scavenging ability. In cisplatin-injured human kidney 2 (HK-2) cells, QMLNCs reduced Fe2+ and reactive oxygen species (ROS) accumulation, preserved mitochondrial membrane potential. Mechanistically, Western blot analysis indicated that QMLNCs could restore the protein levels of SLC7A11, GPX4, and FTH-1, which are key mediators of ferroptosis resistance. In macrophages, QMLNCs suppressed M1 polarization, promoted M2 polarization, and reduced tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), and nitric oxide (NO) production. In vivo, QMLNCs preferentially accumulated in injured kidneys and significantly alleviated renal dysfunction in both glycerol-induced and cisplatin-induced AKI models, as indicated by decreased serum creatinine, blood urea nitrogen, MDA and pro-inflammatory cytokines. Overall, QMLNCs integrate renal tubular targeting, ROS scavenging, ferroptosis inhibition, and inflammation modulation into a single metal-natural product nanoplatform, offering a promising strategy for multimodal AKI therapy.<\/jats:p>","DOI":"10.1021\/acsami.6c15192","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:01:34Z","timestamp":1791367294000},"page":"55962-55975","source":"Crossref","is-referenced-by-count":0,"title":["Lysozyme-Associated Quercetin\u2013Manganese Nanocomposites for Kidney-Targeted Antiferroptotic Therapy of Acute Kidney Injury"],"prefix":"10.1021","volume":"18","author":[{"given":"Yanzhu","family":"Sun","sequence":"first","affiliation":[{"name":"Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiting","family":"Li","sequence":"additional","affiliation":[{"name":"China Medical University , , ,","place":["Liaoning, China, 110122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfei","family":"Han","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"China Medical University , , ,","place":["Liaoning, China, 110122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-0721","authenticated-orcid":true,"given":"Hongzhuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]},{"name":"Ministry of Education, Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-4573","authenticated-orcid":true,"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]},{"name":"Ministry of Education, Shenyang Pharmaceutical University , , , ,","place":["Shenyang, Liaoning, P. R. China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"issue":"4","key":"2026102609065811100_cit1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nrneph.2017.2","article-title":"Acute Kidney Disease and Renal Recovery: Consensus Report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup","volume":"13","author":"Chawla","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"issue":"10474","key":"2026102609065811100_cit2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0140-6736(24)02385-7","article-title":"Acute Kidney Injury","volume":"405","author":"Ostermann","year":"2025","journal-title":"Lancet"},{"issue":"3","key":"2026102609065811100_cit3","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41581-025-01030-4","article-title":"The Global Epidemiology of Acute Kidney Injury: Challenges and Opportunities","volume":"22","author":"Cerda","year":"2026","journal-title":"Nat. Rev. Nephrol."},{"issue":"10","key":"2026102609065811100_cit4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41581-019-0184-x","article-title":"Molecular Nephrology: Types of Acute Tubular Injury","volume":"15","author":"Desanti De Oliveira","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"issue":"3","key":"2026102609065811100_cit5","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nrneph.2018.5","article-title":"Macrophage Extracellular Traps in Rhabdomyolysis-Induced AKI","volume":"14","author":"Allison","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"issue":"1","key":"2026102609065811100_cit6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41581-022-00631-7","article-title":"Cisplatin Nephrotoxicity: New Insights and Therapeutic Implications","volume":"19","author":"Tang","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"issue":"5","key":"2026102609065811100_cit7","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1007\/s00204-025-04041-z","article-title":"The Role of Redox Signaling in Mitochondria and Endoplasmic Reticulum Regulation in Kidney Diseases","volume":"99","author":"Aparicio-Trejo","year":"2025","journal-title":"Arch. 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Nephrol."},{"issue":"1","key":"2026102609065811100_cit9","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-01979-4","article-title":"The Emerging Role of Regulated Cell Death in Ischemia and Reperfusion-Induced Acute Kidney Injury: Current Evidence and Future Perspectives","volume":"10","author":"Li","year":"2024","journal-title":"Cell Death Discov."},{"issue":"9","key":"2026102609065811100_cit10","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06144-w","article-title":"Emerging Significance and Therapeutic Targets of Ferroptosis: A Potential Avenue for Human Kidney Diseases","volume":"14","author":"Li","year":"2023","journal-title":"Cell Death Dis."},{"key":"2026102609065811100_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118358","article-title":"The Role of Quercetin in the Treatment of Kidney Diseases: A Comprehensive Review","volume":"190","author":"Chen","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"2026102609065811100_cit12","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.bbrc.2022.03.159","article-title":"Therapeutic Effect of Quercetin Polymeric Nanoparticles on Ischemia\/Reperfusion-Induced Acute Kidney Injury in Mice","volume":"608","author":"Huang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"1","key":"2026102609065811100_cit13","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12951-025-03210-7","article-title":"Nanomedicine\u2019s Shining Armor: Understanding and Leveraging the Metal-Phenolic Networks","volume":"23","author":"Tang","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"2026102609065811100_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2025.102822","article-title":"Designing Metal\u2013Phenolic Networks in Biomedicine","volume":"45","author":"Lin","year":"2025","journal-title":"Appl. Mater. 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