Abstract

Background Delaying or even reversing liver fibrosis is a research priority in the field of chronic liver disease. The latest evidence of neutrophil extracellular traps (NETs) promoting liver fibrosis reveals a new perspective for anti-hepatic fibrosis therapeutic research, which is currently lacking in clinical evidence with precise intervention strategies. Results In this study, we first compared the elevated NETs index in the peripheral blood of patients with liver fibrosis and healthy individuals, and also characterized the accumulation of NETs in different stages of liver fibrosis models. Subsequently, we designed a liposomal nanoparticle cRGD-QR-Lipo capable of targeting and piggybacking on neutrophils, and selected a quercetin dose with optimal inhibitory effect on NETs for the encapsulated delivery. Compared with conventional NETs-degrading drugs, this system is able to “actively block” the production of NETs. The results demonstrated that cRGD-QR-Lipo showed good biocompatibility, targeting, and effective anti-hepatic fibrosis efficacy. The present study further revealed that the mechanism of anti-hepatic fibrosis effect of cRGD-QR-Lipo may be related to its regulation of IL-6/STAT3 signaling pathway. Conclusions cRGD-QR-Lipo represents a novel neutrophil-targeted strategy to suppress NETosis, providing a promising therapeutic approach against hepatic fibrosis.