Targeted co-delivery of IL-10 and catalase for cooperative therapeutic effect on acute kidney injury

Kidney disease has emerged as a significant public health concern, affecting approximately 10 % of adults worldwide. Especially, acute kidney injury (AKI) increases in-hospital morbidity and mortality. This study introduces a dual-therapeutic strategy combining interleukin-10 (IL-10), an anti-inflammatory cytokine, and catalase (CAT), a reactive oxygen species (ROS)-scavenging enzyme, for the treatment of inflammatory kidney injury. A kidney-targeting peptide-conjugated, Pluronic-based nanocarrier (K-NC) was developed to enable the co-delivery and sustained release of IL-10 and CAT. Compared to no-ligand conjugated NC, K-NC was selectively accumulated in the damaged kidneys while reducing liver accumulation<i>. In vitro</i>, CAT effectively reduced ROS levels in tubular epithelial cells, while IL-10 suppressed inflammatory cytokine expression and promoted M2 macrophage polarization<i>. In vivo</i>, co-delivery of IL-10 and CAT using K-NC resulted in significantly enhanced therapeutic effects on AKI compared to single delivery of IL-10 or CAT using K-NC (IL-10@K-NC or CAT@K-NC), or co-delivery of IL-10 and CAT using no-ligand conjugated NC (IL-10/CAT@NC) by showing reduced levels of serum creatinine and BUN, reduced reactive oxygen species, reduced pro-inflammatory cytokine expression, inhibited M1 macrophage polarization, and promoted M2 macrophage polarization in the kidney. This study not only presents a promising approach for the treatment of kidney inflammation but is also the first report demonstrating enhanced therapeutic effects through a combination of an antioxidant enzyme with an anti-inflammatory cytokine.