Application of Deacetylated Poly-N-Acetyl Glucosamine Nanoparticles for the Delivery of miR-126 for the Treatment of Cecal Ligation and Puncture-Induced Sepsis

Inflammation
Joy N Jones BuieHongkuan Fan

Abstract

Sepsis is an acute inflammatory syndrome in response to infection. In some cases, excessive inflammation from sepsis results in endothelial dysfunction and subsequent increased vascular permeability leading to organ failure. We previously showed that treatment with endothelial progenitor cells, which highly express microRNA-126 (miR-126), improved survival in mice subjected to cecal ligation and puncture (CLP) sepsis. miRNAs are important regulators of gene expression and cell function, play a major role in endothelial homeostasis, and may represent an emerging therapeutic modality. However, delivery of miRNAs to cells in vitro and in vivo is challenging due to rapid degradation by ubiquitous RNases. Herein, we developed a nanoparticle delivery system separately combining deacetylated poly-N-acetyl glucosamine (DEAC-pGlcNAc) polymers with miRNA-126-3p and miRNA-126-5p and testing these combinations in vitro and in vivo. Our results demonstrate that DEAC-pGlcNAc polymers have an appropriate size and zeta potential for cellular uptake and when complexed, DEAC-pGlcNAc protects miRNA from RNase A degradation. Further, DEAC-pGlcNAc efficiently encapsulates miRNAs as evidenced by preventing their migration in an agarose gel. The DEAC...Continue Reading

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Citations

Dec 22, 2019·International Journal of Molecular Sciences·Giuseppina Emanuela GriecoGuido Sebastiani
Dec 15, 2020·World Journal of Stem Cells·Hui-Kang XuCharlie Xiang
Jul 22, 2021·International Journal of General Medicine·Dong JinJie-Sheng Wang

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Methods Mentioned

BETA
dynamic light scattering
electrophoresis
PCR
electrophoretic mobility shift assay
Fluorescent microscopy
transmission electron microscopy

Software Mentioned

image J
GraphPad Prism

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