Size Effect of Nanoparticleson Targeting InjuredKidneys for Enhanced Intervention in Acute Kidney Injury

Abstract Nanoparticles show great potential for the management of acute kidney injuries (AKIs). It is well known that nanoparticle size plays a critical role in targeting renal tubules due to the pore structure and kidney filtration threshold (KFT) of the glomerulus. However, AKI can compromise the physiological barriers, which might render the established KFT (∼6 nm) and size laws under healthy conditions not applicable in AKI conditions. Reinvestigating the nanoparticle size effect on targeting injured kidneys is thus essential for developing efficacious AKI nanomedicine. Herein, using different-sized gold nanoparticles (AuNPs) ranging from 4 to 60 nm as a model of renal nanomedicine, we discovered that the KFT for AuNPs expands from ∼6 nm to ∼10–40 nm under rhabdomyolysis-induced AKI conditions. After loading curcumin, a natural antioxidant, into 5, 16, and 60 nm AuNPs to compare their efficacies against AKI, we found that 5 and 16 nm AuNPs both effectively delivered drugs into renal tubules, resulting in their equal therapeutic performance and significantly better efficacy than 60 nm ones, further validating the enlarged KFT under AKI. Our results provide valuable insights for size engineering of nanomedicine for better AKI management and enable a deeper understanding of AKI renal physiology at the nanoscale.