Gold Nanoparticles Carrying Mannose-Binding Lectin and Inflammatory Cytokine Antibodies Improve Sepsis Survival by Modulating Immunity and Reducing Pathogens.

Abstract

Sepsis is a systemic inflammatory response syndrome caused by infection, and early management of both the infection and the excessive inflammatory response is key to its treatment. In this study, we designed a nanoformulation, termed AuNPs-Mixed, to control bacterial infection and modulate the excessive inflammatory response. AuNPs-Mixed was prepared by equimolarly combining four nanoparticle formulations, each consisting of gold nanoparticles (AuNPs) conjugated separately with mannose-binding lectin (MBL) and three different antibodies targeting pro-inflammatory cytokines: interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α). MBL facilitates the targeted recognition of pathogenic bacteria, while the cytokine-specific antibodies aim to reduce the levels of inflammatory cytokines. The formulation was administered to septic mice for 72 h. The results showed that, compared to the groups treated with AuNPs alone, AuNPs carrying MBL (AuNPs-MBL), and the blank control group, mice receiving the AuNPs-Mixed treatment exhibited significantly lower bacterial loads in the blood, liver, spleen, and kidneys (p < 0.05), reduced levels of inflammatory cytokines, less organ damage, and markedly higher survival rates (p < 0.05). Fluorescence confocal microscopy confirmed that the AuNPs-MBL preparation could bind to Escherichia coli, the primary infectious agent in the sepsis model, facilitating subsequent phagocytosis by macrophages. In the acute toxicity study, no significant differences were observed in body weight, complete blood cell counts, or histopathological analysis of major organs in mice over 7 days (p > 0.05). In conclusion, this study demonstrates that the AuNPs-Mixed formulation effectively reduces bacterial loads in blood and organs, lowers inflammatory cytokine levels, mitigates organ damage, and significantly improves survival rates while showing no evident acute toxicity in mice.