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Liver Regeneration

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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
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Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications

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Published on: November 17, 2015

Cell Subtypes Within the Liver Microenvironment Differentially Interact with Lipid Nanoparticles.

Cory D Sago^1,2, Brandon R Krupczak^1,2, Melissa P Lokugamage¹

¹Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA USA.

Cellular and Molecular Bioengineering

|November 14, 2019

Summary

Lipid nanoparticles (LNPs) deliver nucleic acids to liver cells, but functional delivery varies by cell type. Biodistribution alone does not predict effective mRNA delivery in vivo.

Keywords:

Drug delivery Endothelial cell Kupffer cell Microenvironment siRNA

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Area of Science:

Biomedical Engineering
Nanomedicine
Hepatology

Background:

Lipid nanoparticles (LNPs) preferentially accumulate in the liver.
Mechanisms of LNP delivery to hepatocytes are known, but delivery to other liver cells remain unclear.
Subsets of Kupffer cells and hepatic endothelial cells exhibit unique gene expression and phenotypes.

Purpose of the Study:

To investigate how different liver cell subtypes interact with lipid nanoparticles (LNPs).
To determine if Kupffer and hepatic endothelial cell subsets differentially interact with LNPs.
To compare nucleic acid biodistribution and functional mRNA delivery across liver cell types.

Main Methods:

Quantified nucleic acid biodistribution of two clinically relevant LNPs in vivo.
Assessed functional mRNA delivery within the liver microenvironment using LNPs.
Utilized single-cell profiling data to identify relevant cell subtypes.

Main Results:

LNPs delivered nucleic acids to Kupffer cells and liver endothelial cells as efficiently as hepatocytes.
Functional mRNA delivery was higher in liver endothelial cells compared to hepatocytes.
LNPs showed differential accumulation in specific Kupffer and endothelial cell subsets.

Conclusions:

Liver microenvironmental cell subsets interact differently with nanoparticles in vivo, impacting LNP delivery.
Nucleic acid biodistribution is insufficient to predict functional mRNA delivery in vivo.
Targeting specific liver cell subsets may enhance LNP-based therapies.