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Bacterial Membrane Coating Potentiates Lipid Nanoparticles for mRNA Delivery

Rui Wang1, Lin Bao1, Yiyan Yu1

  • 1Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K. C. Chien and Peter Farrell Collaboratory, University of California─San Diego, La Jolla, California 92093, United States.

Nano Letters
|November 24, 2025
PubMed

Insights

Researchers created hybrid nanoparticles by coating lipid nanoparticles (LNPs) with bacterial outer membrane vesicles (OMVs). This OMV-LNP platform enhances messenger RNA (mRNA) delivery and boosts immune responses for potent vaccine development.

Area of Science:

  • Nanotechnology
  • Immunology
  • Vaccinology

Background:

  • Bacterial outer membrane vesicles (OMVs) are immunostimulatory, carrying antigens and pathogen-associated molecular patterns (PAMPs).
  • Lipid nanoparticles (LNPs) are a successful platform for messenger RNA (mRNA) delivery, crucial for mRNA vaccines.

Purpose of the Study:

  • To develop a hybrid nanoparticle, OMV-coated LNPs (OMV-LNPs), combining LNP delivery efficiency with OMV immunogenicity.
  • To enhance gene delivery and vaccine efficacy using this novel OMV-LNP platform.

Main Methods:

  • Generated OMV-LNPs encapsulating dengue virus (DENV) mRNA (OMV-LNPmRNA) using Escherichia coli-derived OMVs and DENV E80 protein.
  • Evaluated nanoparticle uptake by immune cells, cytosolic mRNA delivery, dendritic cell maturation, and cytokine production in vitro.
  • Assessed antibody titers in AG129 mice following OMV-LNPmRNA administration.

Main Results:

  • OMV-LNPs showed improved uptake by lymph-node immune cells and enhanced cytosolic mRNA delivery.
  • Demonstrated robust in vitro dendritic cell maturation and proinflammatory cytokine production.
  • OMV-LNPmRNA elicited significantly higher DENV-neutralizing antibody titers in mice compared to conventional LNPs.

Conclusions:

  • OMV-LNPs represent a versatile and potent platform for effective mRNA vaccine delivery.
  • This hybrid nanoparticle approach enhances immune cell interaction and mRNA delivery for improved vaccine efficacy.
Keywords:
bacterial outer membranecellular nanoparticledengue vaccinelipid nanoparticlemRNA delivery

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