Spleen-selective co-delivery of mRNA and TLR4 agonist-loaded LNPs for synergistic immunostimulation and Th1 immune responses

Mar 27, 2023Journal of controlled release : official journal of the Controlled Release Society

Targeted delivery of mRNA and immune-activating molecules to the spleen to boost immune responses

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Abstract

Spleen-selective mRNA vaccines induced a potent antigen-specific cytotoxic T cell immune response and prevented tumor growth in a mouse model.

  • Spleen-targeted delivery of unmodified mRNA and TLR agonists resulted in a persistent antitumor cellular immune response.
  • Lipid nanoparticles co-loaded with ovalbumin-coding mRNA and TLR4 agonists effectively facilitated tissue-specific mRNA expression in the spleen.
  • The combination of mRNA antigens and TLR agonists enhanced Th1 immune responses by activating multiple Toll-like receptors.
  • In a prophylactic mouse model, the vaccine prevented the growth of EG.7-OVA tumors and provided immune memory protection.
  • The treatment also delayed tumor growth in subcutaneously transplanted lymphoma and reduced lung metastasis of melanoma.

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