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

Soracha Thamphiwatana(University of California San Diego), Pavimol Angsantikul(University of California San Diego), Tamara Escajadillo(University of California San Diego), Qiangzhe Zhang(University of California San Diego), Joshua Olson(University of California San Diego), Brian T. Luk(University of California San Diego), Sophia Zhang(University of California San Diego), Ronnie H. Fang(University of California San Diego), Weiwei Gao(University of California San Diego), Victor Nizet(University of California San Diego), Liangfang Zhang(University of California San Diego)
Proceedings of the National Academy of Sciences
October 9, 2017
Cited by 552Open Access
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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.


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