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

作者：Soracha Thamphiwatana, Pavimol Angsantikul, Tamara Escajadillo, Qiangzhe Zhang, Joshua Olson, Brian T. Luk, Sophia Zhang, Ronnie H. Fang, Weiwei Gao, Victor Nizet, Liangfang Zhang · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1714267114 · 被引用次数：566 · 研究领域：Immune Response and Inflammation、Immune cells in cancer、S100 Proteins and Annexins

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.