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A Novel Immune-Modulating Nanodrug Enhances Liver-Targeted mRNA Delivery
Daniel Luo1,2, Dandan Guo1,3, Minghao Luo1
1Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, United States.
Molecular Pharmaceutics
|March 13, 2026
Summary
A novel nanodrug (TD ND) effectively reduces inflammation and enhances therapeutic mRNA delivery to liver cells. This approach improves liver function and boosts the efficacy of mRNA treatments for inflammatory liver diseases.
Area of Science:
- Biotechnology
- Nanomedicine
- Immunology
Background:
- Inflammatory liver diseases disrupt liver homeostasis, necessitating therapeutic interventions.
- Therapeutic mRNA delivery via lipid nanoparticles (LNPs) is promising but hindered by inflammation-induced downregulation of gene expression and LNP immunogenicity.
- Existing treatments may not adequately address inflammation's impact on therapeutic efficacy.
Purpose of the Study:
- To investigate a novel immune-modulating telodendrimer nanodrug (TD ND) for inhibiting inflammation and enhancing mRNA delivery in liver cells.
- To evaluate the efficacy of TD ND in reducing inflammation and improving LNP-mediated mRNA delivery in vitro and in vivo.
- To compare the anti-inflammatory and liver-protective effects of TD ND with conventional steroid drugs.
Main Methods:
- Testing TD ND in mouse and human immune cells, liver cell lines, and primary human hepatocytes (PHH) to assess its anti-inflammatory effects.
- Evaluating TD ND's impact on endotoxin-induced inflammation and cell proliferation.
- Assessing the enhancement of mRNA/LNP delivery efficiency in human monocytes and PHH using TD ND.
- Comparing TD ND's efficacy against steroid drugs in a mouse model of endotoxin-induced inflammation and liver dysfunction.
Main Results:
- TD ND effectively inhibited both endogenous and lipopolysaccharide (LPS)-induced inflammation in liver cells.
- TD ND treatment improved cell proliferation in cultured liver cells.
- Significant enhancement in mRNA/LNP delivery efficiency was observed in vitro in human monocytes and PHH.
- TD ND demonstrated superior anti-inflammatory effects and liver function preservation compared to steroid drugs in mice.
Conclusions:
- The novel TD ND is a potent inhibitor of inflammation in liver cells.
- TD ND significantly enhances the efficiency of LNP-mediated mRNA delivery, overcoming inflammation-associated barriers.
- TD ND shows promise as an effective adjuvant therapy to improve mRNA delivery and treatment outcomes for inflammatory liver diseases.
