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Cell Subtypes Within the Liver Microenvironment Differentially Interact with Lipid Nanoparticles.
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2019-05-08 , DOI: 10.1007/s12195-019-00573-4 Cory D Sago 1, 2 , Brandon R Krupczak 1, 2 , Melissa P Lokugamage 1 , Zubao Gan 1 , James E Dahlman 1
中文翻译:
肝脏微环境中的细胞亚型与脂质纳米颗粒有不同的相互作用。
更新日期:2019-05-08
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2019-05-08 , DOI: 10.1007/s12195-019-00573-4 Cory D Sago 1, 2 , Brandon R Krupczak 1, 2 , Melissa P Lokugamage 1 , Zubao Gan 1 , James E Dahlman 1
Affiliation
Introduction
Lipid nanoparticles (LNPs) tend to accumulate in the liver due to physiological factors. Whereas the biological mechanisms that promote LNP delivery to hepatocytes have been reported, the mechanisms that promote delivery to other cell types within the liver microenvironment are poorly understood. Single cell profiling studies have recently identified subsets of Kupffer cells and hepatic endothelial cells with distinct gene expression patterns and biological phenotypes; we hypothesized these subtypes would differentially interact with nanoparticles.Methods
To test the hypothesis, we quantified nucleic acid (i) biodistribution and (ii) functional mRNA delivery within the liver microenvironment using two clinically relevant LNPs in vivo.Results
We found that these LNPs distribute nucleic acids distribute to Kupffer cells and liver endothelial cells as efficiently as they distribute to hepatocytes, yet result in more functional mRNA delivery to endothelial cells. Additionally, we found these LNPs differentially accumulate in Kupffer and endothelial cell subsets.Conclusions
These data suggest subsets of liver microenvironmental cells can differentially interact with nanoparticles in vivo, thereby altering LNP delivery. More generally, the data suggest that nucleic acid biodistribution is not sufficient to predict functional nucleic acid delivery in vivo.中文翻译:
肝脏微环境中的细胞亚型与脂质纳米颗粒有不同的相互作用。