Induction of Metabolic Reprogramming in Kidney by Singlet Diradical Nanoparticles

Abstract 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.