Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine with High Antigen Presentation Efficiency and Immunomodulatory Capability

Feb 6, 2024Angewandte Chemie (International ed. in English)

Mannose-coated lipid nanoparticles for mRNA cancer vaccines that boost antigen display and immune response

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Abstract

Intramuscular injection of the targeted mRNA vaccine STLNPs-Man results in a four-fold higher uptake by dendritic cells compared to commercially used lipid nanoparticles.

Targeting dendritic cells using mannose receptor-mediated endocytosis enhances mRNA delivery.
The STLNPs-Man@mRNA vaccine shows comparable antitumor efficacy with one-fifth the dosage of traditional mRNA vaccines.
Reduced side effects are associated with the lower dosage of the STLNPs-Man@mRNA vaccine.
The STLNPs-Man@mRNA vaccine downregulates a protein associated with T cell inhibition, potentially improving antitumor responses.

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Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNA) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAsignificantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAexhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy. OVA OVA OVA

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Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine with High Antigen Presentation Efficiency and Immunomodulatory Capability

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