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

• DOI: 10.1073/pnas.1714267114
• Publication Date: 2017-10-09T19:00:31Z
• Authors: Soracha Thamphiwa...; Pavimol Angsantikul; Tamara Escajadillo; Qiangzhe Zhang; Joshua Olson; Brian T. Luk; Sophia Zhang; Ronnie H. Fang; Weiwei Gao; Victor Nizet; Liangfang Zhang
• Keywords: Lipopolysaccharides; Male; proinflammatory cytokine; Lipoproteins; Medical Biotechnology; 610; Bioengineering; Bacteremia; Cell Line; sepsis; Mice; 03 medical and health sciences; biomimetic nanoparticle; Sepsis; Nanotechnology; 2.1 Biological and endogenous factors; Animals; detoxification; Escherichia coli Infections; Mice, Inbred ICR; 0303 health sciences; Biomedical and Clinical Sciences; Inflammatory and immune system; Macrophages; lipopolysaccharide; Cell Membrane; Hematology; Inbred ICR; 3. Good health; Endotoxins; Toll-Like Receptor 4; Infectious Diseases; Good Health and Well Being; Cytokines; Nanoparticles; Infection

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.