Reversing Acute Kidney Injury through Coordinated Interplay of Anti‐Inflammation and Iron Supplementation

Abstract 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, herein, an ultrasmall Fe₃O₄ nanoparticle is used 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 Fe₃O₄ 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 the cell membrane. It is demonstrated that NMN‐loaded Fe₃O₄ nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In‐depth studies indicate that a well‐timed iron replenishment following anti‐inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti‐ROS (reactive oxygen species), anti‐inflammation, or even iron elimination.