Natural Macrophage Membrane-Coated Nanoparticles as a Multifaceted Sepsis Therapeutic to Sequester Inflammatory and Toxic Mediators.

Bacterial sepsis is a life-threatening immune dysregulation triggered by bacterial infection and propagated by a dysfunctional host response, culminating in systemic tissue damage and multiorgan failure. In the United States, sepsis results in the hospitalization of more than one million patients annually and accounts for nearly one in three hospital deaths. Despite decades of efforts to develop immunoregulatory sepsis therapies, no clinically approved treatments exist. Recent advances in nanotechnology have introduced innovative approaches, including cellular nanodecoys synthesized from natural macrophage membranes coated onto polymeric nanoparticle cores. Here we introduce a human macrophage membrane-derived drug candidate, CTI-111, capable of sequestering soluble microbial toxins, drivers of inflammation, and pro-inflammatory cytokines from multiple sources. Therapeutic administration of CTI-111 reduces inflammation and improves survival in multiple murine sepsis models. We further demonstrate that CTI-111 can bind multiple sepsis-associated human cytokines in the complex environment of septic serum ex vivo. Together, these findings highlight the potential of CTI-111 as a multifaceted therapy for sepsis.