Xinyao Luo , Shanshan Chen , Zhuyun Zhang , Yiyuan Wang , Yupei Li , Wenjie Shao , Hongju Zhou , Baihai Su , Chong Cheng
{"title":"铱簇/铪-卟啉框架异质结用于生物催化ros清除和急性肾损伤缓解","authors":"Xinyao Luo , Shanshan Chen , Zhuyun Zhang , Yiyuan Wang , Yupei Li , Wenjie Shao , Hongju Zhou , Baihai Su , Chong Cheng","doi":"10.1016/j.jconrel.2025.113993","DOIUrl":null,"url":null,"abstract":"<div><div>The clinical treatments of acute kidney injury (AKI) face significant challenges from complex microenvironments caused by excessive reactive oxygen species (ROS) and severe inflammation. Up to now, effective treatments remain scarce. In this study, we propose a versatile and effective biocatalytic heterojunction, Ir@Hf-TCPP, developed by growing iridium clusters on hafnium-tetrakis (4-carboxyphenyl) porphyrin (Hf-TCPP) through a readily accessible solvothermal approach. The metal‑oxygen bonds between the Ir clusters and Hf-TCPP ensure structural stability and adequate exposure of the surface active sites. Moreover, such interfacial features can efficiently accommodate the electronic structure of Ir@Hf-TCPP through the electronic interaction of the formed Hf-O-Ir bridge and boost the biocatalytic antioxidase-like performance. As a result, the optimized Ir@Hf-TCPP antioxidant demonstrates robust and broad-spectrum ROS scavenging performance, providing cytoprotective effects by enhancing endogenous antioxidant defense and maintaining mitochondrial homeostasis in renal tubular epithelia. In a murine rhabdomyolysis-induced AKI model, Ir@Hf-TCPP significantly ameliorated kidney injury by suppressing the MEKK1/JNK/p38 signaling pathway. Additionally, the Ir@Hf-TCPP exhibited effective renal accumulation and excellent biocompatibility <em>in vivo</em>. The beneficial impact and favorable biocompatibility of Ir@Hf-TCPP will promote the management of AKI and other ROS-associated diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 113993"},"PeriodicalIF":10.5000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Iridium cluster/hafnium-porphyrin framework heterojunctions for biocatalytic ROS-scavenging and acute kidney injury alleviation\",\"authors\":\"Xinyao Luo , Shanshan Chen , Zhuyun Zhang , Yiyuan Wang , Yupei Li , Wenjie Shao , Hongju Zhou , Baihai Su , Chong Cheng\",\"doi\":\"10.1016/j.jconrel.2025.113993\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The clinical treatments of acute kidney injury (AKI) face significant challenges from complex microenvironments caused by excessive reactive oxygen species (ROS) and severe inflammation. Up to now, effective treatments remain scarce. In this study, we propose a versatile and effective biocatalytic heterojunction, Ir@Hf-TCPP, developed by growing iridium clusters on hafnium-tetrakis (4-carboxyphenyl) porphyrin (Hf-TCPP) through a readily accessible solvothermal approach. The metal‑oxygen bonds between the Ir clusters and Hf-TCPP ensure structural stability and adequate exposure of the surface active sites. Moreover, such interfacial features can efficiently accommodate the electronic structure of Ir@Hf-TCPP through the electronic interaction of the formed Hf-O-Ir bridge and boost the biocatalytic antioxidase-like performance. As a result, the optimized Ir@Hf-TCPP antioxidant demonstrates robust and broad-spectrum ROS scavenging performance, providing cytoprotective effects by enhancing endogenous antioxidant defense and maintaining mitochondrial homeostasis in renal tubular epithelia. In a murine rhabdomyolysis-induced AKI model, Ir@Hf-TCPP significantly ameliorated kidney injury by suppressing the MEKK1/JNK/p38 signaling pathway. Additionally, the Ir@Hf-TCPP exhibited effective renal accumulation and excellent biocompatibility <em>in vivo</em>. The beneficial impact and favorable biocompatibility of Ir@Hf-TCPP will promote the management of AKI and other ROS-associated diseases.</div></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":\"385 \",\"pages\":\"Article 113993\"},\"PeriodicalIF\":10.5000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365925006145\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365925006145","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Iridium cluster/hafnium-porphyrin framework heterojunctions for biocatalytic ROS-scavenging and acute kidney injury alleviation
The clinical treatments of acute kidney injury (AKI) face significant challenges from complex microenvironments caused by excessive reactive oxygen species (ROS) and severe inflammation. Up to now, effective treatments remain scarce. In this study, we propose a versatile and effective biocatalytic heterojunction, Ir@Hf-TCPP, developed by growing iridium clusters on hafnium-tetrakis (4-carboxyphenyl) porphyrin (Hf-TCPP) through a readily accessible solvothermal approach. The metal‑oxygen bonds between the Ir clusters and Hf-TCPP ensure structural stability and adequate exposure of the surface active sites. Moreover, such interfacial features can efficiently accommodate the electronic structure of Ir@Hf-TCPP through the electronic interaction of the formed Hf-O-Ir bridge and boost the biocatalytic antioxidase-like performance. As a result, the optimized Ir@Hf-TCPP antioxidant demonstrates robust and broad-spectrum ROS scavenging performance, providing cytoprotective effects by enhancing endogenous antioxidant defense and maintaining mitochondrial homeostasis in renal tubular epithelia. In a murine rhabdomyolysis-induced AKI model, Ir@Hf-TCPP significantly ameliorated kidney injury by suppressing the MEKK1/JNK/p38 signaling pathway. Additionally, the Ir@Hf-TCPP exhibited effective renal accumulation and excellent biocompatibility in vivo. The beneficial impact and favorable biocompatibility of Ir@Hf-TCPP will promote the management of AKI and other ROS-associated diseases.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries.
Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.