Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers.

Science Advances
Jianati DawulietiLi Chen

Abstract

Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll-like receptor 9-mediated proinflammatory pathway in severe sepsis progression. Hypothesizing that removing cfDNA would be beneficial for sepsis treatment, we used polyethylenimine (PEI) and synthesized PEI-functionalized, biodegradable mesoporous silica nanoparticles with different charge densities as cfDNA scavengers. These nucleic acid-binding nanoparticles (NABNs) showed superior performance compared with their nucleic acid-binding polymer counterparts on inhibition of cfDNA-induced inflammation and subsequent multiple organ injury caused by severe sepsis. Furthermore, NABNs exhibited enhanced accumulation and retention in the inflamed cecum, along with a more desirable in vivo safety profile. Together, our results revealed a key contribution of cfDNA in severe sepsis and shed a light on the development of NABN-based therapeutics for sepsis therapy, which currently remains intract...Continue Reading

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
lavage
flow cytometry
Transmission electron microscopy
ELISA
transfection
DNA Assay
fluorescence-activated cell sorting
lavages
fluorescence microscopy

Software Mentioned

GraphPad Prism
Quantity One

Related Concepts

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