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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
Summary
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.
