Engineered internal architecture of core-shell lipid nanoparticles promotes efficient mRNA endosomal release

Jan 30, 2026Nature communications

Designed inner structure of lipid nanoparticles helps mRNA escape from cell compartments

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Abstract

Au-LNPs achieve a twofold increase in endosomal escape and ~100-fold greater cytoplasmic mRNA diffusion compared to conventional lipid nanoparticles.

  • Engineering LNPs with ionizable lipid-coated gold nanoparticles creates a more efficient internal structure.
  • This new architecture stabilizes the particles at physiological pH and enhances their performance in acidic environments.
  • Au-LNPs show improved mRNA expression in vitro and increase protein production in vivo by up to sevenfold.
  • These particles also enhance immune responses to SARS-CoV-2 vaccines and improve treatment outcomes in triple-negative breast cancer models.

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Key numbers

Increase in Endosomal Escape Efficiency
Au-LNPs compared to conventional LNPs
~100-fold
Cytoplasmic mRNA Diffusion Enhancement
Au-LNPs compared to conventional LNPs
Increase in Antibody Titers
Au-LNPs vs. conventional LNPs after initial immunization

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