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

• DOI: 10.1002/adma.202404830
• Publication Date: 2024-06-19T11:41:35Z
• Authors: Po‐Kai Luo; Hui‐Min Ho; Min‐Chun Chiang; Li‐An Chu; Ya‐Han Chuang; Ping‐Chiang Lyu; I‐Chen Hu; Wan‐An Chang; Sheng‐Yao Peng; Jayachandran Jaya...; Hsin‐Lung Chen; Ming‐Hsi Huang; Hsing‐Wen Sung
• Keywords: Cancer Immunotherapy; Mesenteric lymph nodes; Cancer vaccine

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