Induction of Metabolic Reprogramming in Kidney by Singlet Diradical Nanoparticles,Advanced Materials

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Induction of Metabolic Reprogramming in Kidney by Singlet Diradical Nanoparticles
Advanced Materials ( IF 27.4 ) Pub Date : 2023-06-09 , DOI: 10.1002/adma.202301338
Lei Ye ₁ , Shengwei Jiang ₂ , Jinlian Hu ₃ , Mingzhe Wang ₁ , Taoyu Weng ₃ , Feng Wu ₁ , Liangyu Cai ₁ , Zhe Sun ₃ , Lan Ma _{1,

2,

4,

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Affiliation

Polycyclic aromatic compounds with an open-shell singlet diradical ground state, namely singlet diradicals, have recently gained attention in the fields of organic electronics, photovoltaics, and spintronics owing to their unique electronic structures and properties. Notably, singlet diradicals exhibit tunable redox amphoterism, which makes them excellent redox-active materials for biomedical applications. However, the safety and therapeutic efficacy of singlet diradicals in biological systems have not yet been explored. Herein, the study presents a newly designed singlet diradical nanomaterial, diphenyl-substituted biolympicenylidene (BO-Ph), exhibiting low cytotoxicity in vitro, non-significant acute nephrotoxicity in vivo, and the ability to induce metabolic reprogramming in kidney organoids. Integrated transcriptome and metabolome analyses reveal that the metabolism of BO-Ph stimulates glutathione (GSH) synthesis and fatty acid degradation, increases the levels of intermediates in the tricarboxylic acid (TCA) and carnitine cycles, and eventually boosts oxidative phosphorylation (OXPHOS) under redox homeostasis. Benefits of BO-Ph-induce metabolic reprogramming in kidney organoids include enhancing cellular antioxidant capacity and promoting mitochondrial function. The results of this study can facilitate the application of singlet diradical materials in the treatment of clinical conditions induced by mitochondrial abnormalities in kidney.

中文翻译：

单线态双自由基纳米粒子诱导肾脏代谢重编程

具有开壳层单线态双自由基基态的多环芳香族化合物，即单线态双自由基，由于其独特的电子结构和性质，近年来在有机电子、光伏和自旋电子学领域受到关注。值得注意的是，单线态双自由基表现出可调节的氧化还原两性，这使得它们成为生物医学应用中优异的氧化还原活性材料。然而，单线态双自由基在生物系统中的安全性和治疗功效尚未得到探索。在此，该研究提出了一种新设计的单线态双自由基纳米材料，即二苯基取代的二亚苯基（BO-Ph），其在体外表现出低细胞毒性，在体内表现出不显着的急性肾毒性，并且能够诱导肾脏类器官代谢重编程。综合转录组和代谢组分析表明，BO-Ph 的代谢刺激谷胱甘肽 (GSH) 合成和脂肪酸降解，增加三羧酸 (TCA) 和肉碱循环中的中间体水平，并最终增强氧化还原作用下的氧化磷酸化 (OXPHOS)体内平衡。BO-Ph 诱导肾脏类器官代谢重编程的好处包括增强细胞抗氧化能力和促进线粒体功能。这项研究的结果可以促进单线态双自由基材料在治疗肾脏线粒体异常引起的临床病症中的应用。

更新日期：2023-06-09

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