A research team led by Prof. ZHANG Zhiping and Prof. KONG Li from School of Pharmacy of Tongji Medical College of HUST has created a breakthrough lipid nanoparticle (LNP) system using vitamin E as a core component. Their innovation demonstrated both superior mRNA delivery capabilities and immune-boosting properties beyond expectation.

The team engineered a novel series of ionizable lipids (VNxCyOz) with vitamin E as the hydrophobic core, attaining an 80% improvement in cellular uptake compared to commercial alternatives like SM102. Apart from delivery efficiency, these vitamin E-derived LNPs spontaneously activated dendritic cells and enhanced antigen presentation – two critical steps in immune response initiation.

In multiple colon cancer models, the system showed remarkable therapeutic effects when delivering interleukin-12 (IL-12) mRNA. The vitamin E-LNP formulation nearly eradicated metastatic liver tumors and accomplished complete remission in peritoneal metastasis models, all without the weight loss typically associated with IL-12 therapies.

The research further revealed the potential to synergistically use the strategy with existing immunotherapies. Combined with PD-L1 blockade, the vitamin E-LNPs amplified anti-tumor immunity by increasing tumor-infiltrating T cells and pro-inflammatory cytokines while promoting dendritic cell maturation.

PhD candidate CUI Kexin served as the lead author of the study, which received support from Wuhan's R&D Program and the National Natural Science Foundation. Industry and academic partners provided critical mRNA materials for the research.