Redox nanomedicine ameliorates chronic kidney disease (CKD) by mitochondrial reconditioning in mice

• Published in: Communications biology Vol. 4; no. 1; p. 1013
• Main Authors: Adhikari, Aniruddha, Mondal, Susmita, Chatterjee, Tanima, Das, Monojit, Biswas, Pritam, Ghosh, Ria, Darbar, Soumendra, Alessa, Hussain, Althakafy, Jalal T., Sayqal, Ali, Ahmed, Saleh A., Das, Anjan Kumar, Bhattacharyya, Maitree, Pal, Samir Kumar
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 14/19; 14/63; 631/154/433; 64/60; 692/308/2778; Animal models; Animals; Aquatic plants; Biology; Biomedical and Life Sciences; Cardiovascular diseases; Cisplatin; Citric acid; Cytokines; Diabetes mellitus; Female; Fibrosis; Homeostasis; Inflammation; Intracellular; Kidney diseases; Life Sciences; Male; Mice; Mitochondria; Mitochondria - physiology; Nanomedicine; Nanoparticles; Nanotechnology; Nephropathy; Neurodegeneration; Oxidation-Reduction; Pathogenesis; Reactive oxygen species; Reactive Oxygen Species - administration & dosage; Renal function; Renal Insufficiency, Chronic - therapy; Structure-function relationships
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02546-8

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that a potential nanomedicine comprising of Mn 3 O 4 nanoparticles duly functionalized with biocompatible ligand citrate (C-Mn 3 O 4 NPs) can maintain cellular redox balance in an animal model of oxidative injury. We developed a cisplatin-induced CKD model in C57BL/6j mice with severe mitochondrial dysfunction and oxidative distress leading to the pathogenesis. Four weeks of treatment with C-Mn 3 O 4 NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis. Adhikari et al. use the redox modulatory abilities of citrate functionalized Mn3O4 nanoparticles to ameliorate oxidative damage in murine disease model of chronic kidney disease (CKD). This nanomedicine works by protecting structural and functional integrity of mitochondria from oxidative injury, reducing intracellular ROS, downregulating pro-inflammatory cytokines and maintaining cellular redox homeostasis.