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‐G1_AMP, are fabricated. It is found that BP‐G1_AMP 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.