肿瘤预防与治疗2024，Vol.37Issue(7)：555-562,8.DOI:10.3969/j.issn.1674-0904.2024.07.002
橙皮素对mRNA疫苗的免疫增强作用及其机制研究
Immunoenhancement Effect of Hesperetin on mRNA Vaccines and Its Mechanism
摘要
Abstract
Objective:To investigate the influence of hes-peretin as an adjuvant of mRNA vaccines on tumor prevention effect and its immune mechanism,and provide new ideas for the development of traditional Chinese medicine and its monomer components as vaccine adjuvants.Methods:Lipid nanoparticles(LNPs)loaded with mRNA and/or hesperetin were pre-pared via microfuidics.Particle size and encapsulation efficiency of complexes were determined once prepared.The uptake and expression of the complexes by dendritic cells were investigated by flow cytometry.C57BL/6 mice were randomly as-signed to the phosphate buffer solution control group(NC group),the hesperetin-LNPs group(Hes group),the ovalbumin(OVA)mRNA-LNPs group(mRNA group)and the hesperetin OVA mRNA-LNPs group(Hes-mRNA group),then were immunized by hypodermically injecting with drugs on day 0 and day 7,respectively.E.G7 OVA cells were subcutaneously inoculated 28 days after the first injection.Tumor volume and survival of the mice were monitored.The levels of IFN-γ in CD4+and CD8+T cells in the lymph nodes of mice were detected by flow cytometry.The concentration of OVA-sIgG in the serum of mice was detected by ELISA.Results:The delivery system was stable and enables the intracellular delivery of mR-NA.The survival time in the Hes group,the mRNA group and the Hes-mRNA group were longer than that in the NC group(P＜0.05,P＜0.05 and P＜0.001);mRNA group and Hes-mRNA group showed a significant delay of tumor growth compared to the NC group(P＜0.05).Tumor growth rate and survival in the Hes-mRNA group were significantly higher than those in the mRNA group(P＜0.05).Compared with the NC group,the levels of IFN-γ+CD4+and IFN-γ+CD8+T cells signifi-cantly increased in the mRNA group and the Hes-mRNA group(P＜0.05).Compared with the NC group,the concentration of OVA-sIgG in the serum of mice in the Hes group significantly increased(P＜0.001).Conclusion:Hesperetin,as Chi-nese medicine adjuvant,can be stably added into the mRNA-LNPs system by electrostatic adsorption,and can prevent tumor and induce humoral immunity in mice.The combined use of hesperetin and mRNA can simultaneously activate both cellular immunity and humoral immunity,effectively delay tumor growth,and enhance the effect of tumor prevention.关键词
橙皮素/mRNA/预防/肿瘤/免疫Key words
Hesperetin/mRNA/Prevention/Tumor/Immune分类
医药卫生引用本文复制引用
季阿芳,王斯琦,蒋瑜,刘海青,娄家淇,程军平..橙皮素对mRNA疫苗的免疫增强作用及其机制研究[J].肿瘤预防与治疗,2024,37(7):555-562,8.基金项目
This study was supported by grants from Suzhou Pharmaceutical Association(No.SKYXD2022033).常州四药临床药学科研基金资助项目(编号:SKYXD2022033) （No.SKYXD2022033）
