Design of messenger RNA vaccines based on lipid-polymer hybrid nanoparticles

🥉 Top 5% JournalNov 5, 2025Journal of controlled release : official journal of the Controlled Release Society

Design of messenger RNA vaccines using mixed fat and polymer nanoparticles

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Abstract

Lipid-polymer hybrid nanoparticles (LPNs) loaded with mRNA produced higher spike-specific IgG responses and reduced SARS-CoV-2 load in the nasal cavity compared to traditional lipid nanoparticles (LNPs).

  • The design of LPNs incorporates a biocompatible polymer, ionizable lipid, and helper lipid, allowing for effective mRNA delivery.
  • Key factors influencing mRNA delivery include total lipid content and the ionizable lipid:mRNA weight ratio.
  • LPNs demonstrated localized protein expression at the injection site, unlike traditional LNPs which expressed protein in the liver.
  • Lower flow rate ratios during formulation resulted in a polymer core-shell hybrid structure, while higher ratios led to a mix of multi-lamellar vesicles and nanospheres.
  • In mouse models, LPNs elicited CD8 T-cell and antibody responses comparable to those from LNPs.

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