pH‐Responsive β‐Glucans‐Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy

🥇 Top 1% JournalJun 19, 2024Advanced materials (Deerfield Beach, Fla.)

pH-Sensitive β-Glucan-Coated mRNA Nanoparticles as an Oral Vaccine to Boost Cancer Immunotherapy

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mRNA Technology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Oral β-glucan complexed mRNA vaccines (βGlus/mRNA@LNPs) show effective uptake by immune cells in the gastrointestinal tract.

The formulation is designed to protect mRNA from degradation in the gastrointestinal environment by responding to pH changes.
Upon oral administration to tumor-bearing mice, the vaccine is taken up by intestinal immune cells, bypassing liver accumulation.
The uptake of βGlus/mRNA@LNPs initiates antigen-specific immune responses, leading to the stimulation of T cells.
The vaccine demonstrates safety with no significant inflammatory reactions reported.

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mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with β-glucans (βGlus), a potential adjuvant for vaccines, encapsulated within LNPs (βGlus/mRNA@LNPs). The βGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, βGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral βGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration.

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