Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management

TLDR

Endotoxins released during Gram‑negative bacterial sepsis drive disease progression, yet no effective methods exist to neutralize the diverse endotoxins from different bacterial strains. We aim to evaluate a macrophage‑like nanoparticle that sequentially neutralizes endotoxins and sequesters proinflammatory cytokines for sepsis control. The biomimetic nanoparticles display a macrophage‑cell surface, enabling them to bind endotoxins and cytokines. This detoxification strategy offers a first‑in‑class sepsis treatment that could improve patient outcomes.

Abstract

Significance Clinical evidence has indicated that the systemic spread of endotoxins from septic infection plays a crucial role in the pathogenesis of Gram-negative bacterial sepsis. However, currently there are no effective ways to manage the diverse endotoxins released by different bacterial genus, species, and strain. Herein, we demonstrate the therapeutic potential of a macrophage-like nanoparticle for sepsis control through a powerful two-step neutralization process: endotoxin neutralization in the first step followed by cytokine sequestration in the second step. The biomimetic nanoparticles possess an antigenic exterior identical to macrophage cells, thus inheriting their capability to bind to endotoxins and proinflammatory cytokines. This detoxification strategy may provide a first-in-class treatment option for sepsis and ultimately improve the clinical outcome of patients.