Why do lipid nanoparticles target the liver? Understanding of biodistribution and liver-specific tropism.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic biology and engineering concepts without original human data or systematic review methodology.
PubMed 40104152 · doi:10.1016/j.omtm.2025.101436
What was done
This narrative review summarizes the biological and anatomical mechanisms underlying the biodistribution and liver tropism of lipid nanoparticles (LNPs). It outlines the role of endogenous serum protein adsorption (particularly apolipoprotein E), low-density lipoprotein (LDL) receptor interactions on hepatocytes, hepatic microarchitecture, and therapeutic strategies for optimizing liver and extrahepatic LNP delivery.
What was found
The abstract reports no numerical data. It highlights that LNP liver specificity is mediated primarily by ApoE association facilitating LDL receptor-mediated endocytosis into hepatocytes, combined with uptake and clearance by specialized hepatic cell types.
Why it matters
Clarifying the determinants of natural LNP hepatic homing is critical for improving nucleic acid delivery in liver diseases and for rationally designing modified nanoparticles capable of evading liver clearance to reach non-hepatic targets.
Limits
As a narrative review, it provides no systematic search strategy, risk-of-bias evaluation, or primary empirical data. No quantitative comparative performance metrics across different LNP formulations are presented in the abstract.