Effect of IGF-1C domain-modified nanoparticles on renal ischemia–reperfusion injury in mice

Abstract

Renal ischemia–reperfusion injury (IRI) is a common prerequisite of acute renal injury (AKI) that involves the entire system and induces critical illness. The C domain of insulin-like growth factor-1 (IGF-1C) plays an important role in promoting angiogenesis and enhancing the inflammatory response. However, given the shortcomings of its short half-life and poor stability, the application of IGF-1C is restricted. In the present study, IGF-1C nanoparticles (NP-IGF-1C) were constructed by combining 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide (polye thyleneglycol)](DSPE-PEG-MAL) and IGF-1C through a Michael addition reaction to evaluate the effects of NP-IGF-1C on preventing IRI. In vitro studies have shown that NP-IGF-1C is not cytotoxic and protects cells from oxidative damage. The renal enrichment and biocompatibility of NP-IGF-1C were determined in vivo by connecting fluorescent molecules to NP-IGF-1C for in vivo imaging and pathological staining of important organs. After IRI, renal function decreased, and inflammatory cell infiltration, oxidative stress and apoptosis increased. As expected, NP-IGF-1C reversed these changes, indicating that NP-IGF-1C played a protective role in the process of IRI, which may be mediated by its antioxidant, anti-inflammatory and antiapoptotic activities.

Keywords

• Renal ischemia–reperfusion
• C domain of insulin-like growth factor
• NP-IGF-1C
• acute kidney injury
• antioxidant