pH-Responsive β-Glucans-Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy
Journal
Advanced Materials
Journal Volume
36
Journal Issue
33
Start Page
2404830
ISSN
9359648
Date Issued
2024
Author(s)
Luo, Po-Kai
Ho, Hui-Min
Chiang, Min-Chun
Chuang, Ya-Han
Lyu, Ping-Chiang
Hu, I-Chen
Chang, Wan-An
Peng, Sheng-Yao
Jayakumar, Jayachandran
Chen, Hsin-Lung
Huang, Ming-Hsi
Sung, Hsing-Wen
Abstract
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. © 2024 Wiley-VCH GmbH.
Subjects
cancer immunotherapy
lipid nanoparticle
mRNA vaccine
oral cancer vaccine
β-glucans
Publisher
John Wiley and Sons Inc
Type
journal article