Why do lipid nanoparticles target the liver? Understanding of biodistribution and liver-specific tropism

Lipid nanoparticles (LNPs) are now highly effective transporters of nucleic acids to the liver. This liver-specificity is largely due to their association with certain serum proteins, most notably apolipoprotein E (ApoE), which directs them to liver cells by binding to the low-density lipoprotein (L...

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Published inMolecular therapy. Methods & clinical development Vol. 33; no. 1; p. 101436
Main Authors Hosseini-Kharat, Mahboubeh, Bremmell, Kristen E., Prestidge, Clive A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 13.03.2025
American Society of Gene & Cell Therapy
Elsevier
Subjects
ApoE
apolipoprotein E
biodistribution
lipid nanoparticles
liver targeting
LNPs
Review
therapeutic delivery
lipid nanoparticles
biodistribution
LNPs
apolipoprotein E
ApoE
liver targeting
therapeutic delivery
Online AccessGet full text
ISSN2329-0501
2329-0501
DOI10.1016/j.omtm.2025.101436

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Summary:Lipid nanoparticles (LNPs) are now highly effective transporters of nucleic acids to the liver. This liver-specificity is largely due to their association with certain serum proteins, most notably apolipoprotein E (ApoE), which directs them to liver cells by binding to the low-density lipoprotein (LDL) receptors on hepatocytes. The liver’s distinct anatomy, with its various specialized cell types, also influences how LNPs are taken up from the circulation, cleared, and how effective they are in delivering treatments. In this review, we consider factors that facilitate LNP’s effective liver targeting and explore the latest advances in liver-targeted LNP technologies. Understanding how LNPs are targeted to the liver can help for effective design and optimization of nanoparticle-based therapies. Comprehension of the cellular interaction and biodistribution of LNPs not only leads to better treatments for liver diseases but also delivers insight for directing nanoparticles to other tissues, potentially broadening their range of therapeutic applications. [Display omitted] Lipid nanoparticles (LNPs) preferentially accumulate in the liver through ApoE-mediated LDL receptor binding. This review examines this specificity and explores strategies to enhance targeting, expanding LNP applications beyond hepatic diseases.
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ISSN:2329-0501
2329-0501
DOI:10.1016/j.omtm.2025.101436