Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 43, Pages 11488-11493Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1714267114
Keywords
biomimetic nanoparticle; detoxification; sepsis; lipopolysaccharide; proinflammatory cytokine
Categories
Funding
- National Science Foundation [DMR-1505699]
- Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-14-1-0064]
- NIH [1R01HL125352]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1505699] Funding Source: National Science Foundation
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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 M Phi-NPs, reduced proinflammatory cytokine levels, inhibited bacterial dissemination, and ultimately conferred a significant survival advantage to infected mice. Employing M Phi-NPs as a biomimetic detoxification strategy shows promise for improving patient outcomes, potentially shifting the current paradigm of sepsis management.
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