Multifunctional nanoparticles confers both multiple inflammatory mediators scavenging and macrophage polarization for sepsis therapy

Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Here we designed and constructed a polydopamine-based multifunctional nanoparticle for the treatment of sepsis. These nanoparticles (NPs) are composed of polydopamine (PDA) grafted with cationic polyethyleneimine (PEI). On the one hand, the NPs can utilize the electrostatic interaction to effectively adsorb cfDNA in blood, then effectively inhibiting the activation of toll like receptors (TLRs) and nuclear factor kappa B (NF-κB) pathways induced by cfDNA. On the other hand, the NPs have an immunomodulatory function, which can effectively convert pro-inflammatory macrophage (M1) into anti-inflammatory macrophage (M2), thus reduce the release of inflammatory cytokines and slow down the inflammatory storm of sepsis. In addition, the NPs possess good reactive oxygen species (ROS) scavenging ability. Briefly, the effective treatment of sepsis can be achieved by multiple strategies of effectively capturing the inflammatory triggering factor cfDNA, modulating the polarization of M1 macrophage to M2 macrophage and scavenging ROS, which has a promising clinical application. Sepsis is a serious and life-threatening condition that can arise from an infection, which can lead to organ failure and death in clinic. Abnormally increased cell-free DNA (cfDNA), massive accumulation of reactive oxygen species (ROS), increased pro-inflammatory macrophages and inflammatory cytokines are involved in the development and progression of sepsis. Thus, clearance of these inflammatory mediators and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Multifunctional nanoparticle with cfDNA scavenging, ROS scavenging and immunomodulatory functions can be effective in the treatment of sepsis and have good prospects for clinical application. • Construction of multifunctional nanoparticle based on polydopamine. • Scavenging ROS, capturing cell free DNA, and relieving inflammatory cytokine storm. • Transforming macrophages from M1 to M2 and regulating inflammatory microenvironment. • Reducing multiple organ damage and improving the survival rate of septic mice. • Excellent anti-inflammatory ability and favorable biosafety.