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

IF 10.5 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xinyao Luo , Shanshan Chen , Zhuyun Zhang , Yiyuan Wang , Yupei Li , Wenjie Shao , Hongju Zhou , Baihai Su , Chong Cheng
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引用次数: 0

摘要

急性肾损伤(AKI)的临床治疗面临着由活性氧(ROS)过多和严重炎症引起的复杂微环境的重大挑战。到目前为止,有效的治疗方法仍然很少。在这项研究中,我们提出了一种多功能和有效的生物催化异质结,Ir@Hf-TCPP,通过易于获得的溶剂热方法在铪-四(4-羧基苯基)卟啉(Hf-TCPP)上生长铱簇。Ir簇和Hf-TCPP之间的金属氧键确保了结构的稳定性和表面活性位点的充分暴露。此外,这种界面特征可以通过形成的Hf-O-Ir桥的电子相互作用有效地容纳Ir@Hf-TCPP的电子结构,从而提高生物催化类抗氧化酶的性能。因此,优化后的Ir@Hf-TCPP抗氧化剂显示出强大的广谱ROS清除性能,通过增强内源性抗氧化防御和维持肾小管上皮线粒体稳态来提供细胞保护作用。在小鼠横纹肌溶解诱导的AKI模型中,Ir@Hf-TCPP通过抑制MEKK1/JNK/p38信号通路显著改善肾损伤。此外,Ir@Hf-TCPP在体内表现出有效的肾脏蓄积和良好的生物相容性。Ir@Hf-TCPP的有益作用和良好的生物相容性将促进AKI和其他ros相关疾病的管理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Iridium cluster/hafnium-porphyrin framework heterojunctions for biocatalytic ROS-scavenging and acute kidney injury alleviation

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.
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来源期刊
Journal of Controlled Release
Journal of Controlled Release 医学-化学综合
CiteScore
18.50
自引率
5.60%
发文量
700
审稿时长
39 days
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.
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