Ceria-Zirconia Antioxidant Nanoparticles Attenuate Hypoxia-Induced Acute Kidney Injury by Restoring Autophagy Flux and Alleviating Mitochondrial Damage

Abstract

Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

“…The enzyme-mimetic activity of cerium oxide originates from the redox cycle between Ce (III) and Ce (IV) [ 203 , 204 ]. The CeO 2 crystal on the nanoscale is prone to lose O atoms to form internal vacancies, and part of Ce (IV) is reduced to the unstable Ce (III).…”

Design of Micro- and Nanoparticles: Self-Assembly and Application

“…The low concentration of camptothecin-loaded dendrimers inhibited HCV replication with very low toxicity. The triple combination of carbosilane dendrimers, tenofovir and maraviroc showed potential for inhibiting HIV sexual transmission [130,131,146]. Polyanionic dendrimers comprising the terminal groups sodium carboxylate, hydroxyl and succinamic acid and polycationic dendrimers containing primary amines were used to assess their antiviral activity in MERS-CoV plaque inhibition assays.…”

“…Moreover, due to the variety of loading mechanisms, one is able to tailor the loading technique to the biomaterial of interest; for instance, certain macromolecules or nanoparticles may be sensitive to salt solutions forming the crystal template and, hence, adsorption may be preferred. In addition, freezing-induced loading was recently demonstrated with the loading of TiO 2 nanoparticles [130].…”

“…Both nanoparticulate formulations led to a dose-dependent reduction of HIV-1 antigen production. Nanoparticles as a drug carrier system improved the delivery of antiviral agents to the mononuclear phagocyte system in vivo, overcoming pharmacokinetic problems and enhancing the activities of drugs for the treatment of HIV infection and AIDS [130]. Acyclovir loaded into beta-cyclodextrin-poly(4-acryloylmorpholine) (β-CD-PACM) nanoparticles exhibited significant antiviral activity against two clinical isolates of HSV-1 compared to both the free drug and a soluble β-CD-PACM complex [131].…”

Nanostructured Ceria: Biomolecular Templates and (Bio)applications

“…Another disease model where they have been studied is the non-alcohol-dependent, fatty liver, which is associated with impairment and inflammation of liver tissue, and which was alleviated in a rat model by ceria [ 129 ]. Treatment of hypoxia-induced acute kidney injury had been proposed for ceria combined with zirconia for enhanced radical scavenging activity [ 130 ].…”