Modulation of Unregulated Inflammation-Associated Coagulopathy in Sepsis Using Multifunctional Nanosheets

Abstract

Excessive inflammation-associated unregulated coagulation leads to disseminated intravascular coagulation (DIC) and mortality in patients with sepsis worldwide, and current clinical treatment is unsatisfactory. Recent studies have shown that circulating cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), act as potent pro-inflammation and pro-coagulation agents, revealing a mechanistic link between innate immunity and coagulation. After establishing a definite correlation between cfDNA and dysfunctional inflammation and coagulation disorders in samples from patients with sepsis, a novel 2D, sheet-like, cationic cfDNA scavenger using polyamidoamine (P-G1) and antimicrobial peptides (AMPs) covered with black phosphorus (BP) nanosheets, called BP-G1AMP, are fabricated. It is found that BP-G1AMP significantly suppressed bacterial growth and ameliorated the systemic inflammatory response, associated coagulation disorder, and DIC, resulting in improved survival in a cecal ligation puncture (CLP) mouse sepsis model. This study proposes a novel strategy for fabricating multifunctional nanosheets that can ameliorate inflammation-associated coagulation during sepsis treatment. These findings demonstrate the importance of 2D nanostructures in the construction of multivalent anti-bacterial and anti-coagulation nanoplatforms.