Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093.
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11488-11493. doi: 10.1073/pnas.1714267114. Epub 2017 Oct 9.
Sepsis, resulting from uncontrolled inflammatory responses to bacterial infections, continues to cause high morbidity and mortality worldwide. Currently, effective sepsis treatments are lacking in the clinic, and care remains primarily supportive. Here we report the development of macrophage biomimetic nanoparticles for the management of sepsis. The nanoparticles, made by wrapping polymeric cores with cell membrane derived from macrophages, possess an antigenic exterior the same as the source cells. By acting as macrophage decoys, these nanoparticles bind and neutralize endotoxins that would otherwise trigger immune activation. In addition, these macrophage-like nanoparticles sequester proinflammatory cytokines and inhibit their ability to potentiate the sepsis cascade. In a mouse bacteremia model, treatment with macrophage mimicking nanoparticles, termed MΦ-NPs, reduced proinflammatory cytokine levels, inhibited bacterial dissemination, and ultimately conferred a significant survival advantage to infected mice. Employing MΦ-NPs as a biomimetic detoxification strategy shows promise for improving patient outcomes, potentially shifting the current paradigm of sepsis management.
脓毒症是由细菌感染引起的失控性炎症反应导致的，目前仍是全球性的高发病率和高死亡率疾病。临床上目前缺乏有效的脓毒症治疗方法，主要以支持性治疗为主。在这里，我们报告了一种用于脓毒症管理的巨噬细胞仿生纳米颗粒的开发。这些纳米颗粒由聚合物核外包覆源自巨噬细胞的细胞膜制成，具有与源细胞相同的抗原性外表面。作为巨噬细胞诱饵，这些纳米颗粒可以结合并中和内毒素，否则内毒素会引发免疫激活。此外，这些类似巨噬细胞的纳米颗粒还可以隔离促炎细胞因子，并抑制其增强脓毒症级联反应的能力。在小鼠菌血症模型中，用被称为 MΦ-NPs 的巨噬细胞模拟纳米颗粒治疗可降低促炎细胞因子水平、抑制细菌扩散，最终为感染的小鼠带来显著的生存优势。采用 MΦ-NPs 作为仿生解毒策略显示出改善患者预后的潜力，可能改变目前脓毒症管理的模式。
