Reversing Acute Kidney Injury Through Coordinated Interplay of Anti-inflammation and Iron Supplementation

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD + ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, we herein use an ultra-small Fe 3 O 4 nanoparticle as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD + . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe 3 O 4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD + precursor into renal cells through nicotinamide riboside kinase 1 on cell membrane. It was demonstrated that NMN-loaded Fe 3 O 4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicated that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previously strategies centering on anti-ROS (reactive oxygen species), anti-inflammation or even iron elimination. This article is protected by copyright. All rights reserved