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Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11488-11493. doi: 10.1073/pnas.1714267114. Epub 2017 Oct 9.

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

Author information

1
Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093.
2
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
3
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093.
4
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093.
5
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; vnizet@ucsd.edu zhang@ucsd.edu.
6
Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093; vnizet@ucsd.edu zhang@ucsd.edu.

Abstract

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 Escherichia coli 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.

KEYWORDS:

biomimetic nanoparticle; detoxification; lipopolysaccharide; proinflammatory cytokine; sepsis

PMID:
29073076
PMCID:
PMC5664555
DOI:
10.1073/pnas.1714267114
[Indexed for MEDLINE]
Free PMC Article

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