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, 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.

Automated summary

In this study, ultrasmall Fe3O4 nanoparticles were used as carriers to deliver NMN into renal cells, enhancing mitochondrial function and suppressing inflammation. This approach effectively reversed AKI induced by ischemia reperfusion.