Endotoxin-resistant dendritic cell-derived biomimetic exosomes loaded iridium nanoenzymes for alleviating LPS/D-GalN-induced acute liver failure.

Acute liver failure (ALF) is characterized by a rapid deterioration of liver function in a very short period of time, with a variety of etiological factors and complex pathogenic mechanisms, for which there are no effective therapeutic options. Recent studies have demonstrated that endotoxin-tolerant dendritic cells (ETDC) possess anti-inflammatory properties, typically established in response to repeated lipopolysaccharide (LPS) stimulation. However, living cells are extremely unstablein vivo, so we fabricated exosome mimics (EM), which have higher yields and are simpler and more convenient to handle than conventional exosome properties. Polyvinylpyrrolidone-stabilised iridium nanoparticles (Ir NPs-PVP) have been reported as enzyme mimics with peroxidase- and catalase-like activities and have been shown to be effective in scavenging reactive oxygen species at the cellular level. The aim of this paper is to investigate the palliative effect of ETDC-derived mimetic vesicles loaded with PVP-IrNPs on ALF. The results showed that the combination of ETDC-derived mimetic vesicles and Ir NPs-PVP had anti-inflammatory and antioxidant effects, which effectively alleviated the damage induced by ALF, and is expected to be a novel therapeutic agent for the clinical treatment of ALF.