Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine  

作　　者：Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen Shugang Qin Wen Xiao Qian Zheng Hai Huang Xiawei Wei Yuquan Wei Xiangrong Song 

机构地区：[1]Department of Critical Care Medicine,Department of Clinical Pharmacy,Frontiers Science Center for Disease-related Molecular Network,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041,China [2]West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第3期942-954,共13页药学学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFE0206600);the Sichuan Province Science and Technology Support Program(2021YF-SY0008 and 2020YJ023,China);the Translational Medicine Fund of West China Hospital(CGZH19002,China);the 1.3.5 Project for Disciplines of excellence,West China Hospital,Sichuan University(ZYGD18020/ZYJC18006,China).

摘　　要：The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers.Nevertheless,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA vaccines.To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier,a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate(SA).Intriguingly,the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA,which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of [e-mail] addition,we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting.Finally,we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E.G7-OVA tumor-bearing mice,dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect.Therefore,we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

关 键 词：Negatively charged mRNA vaccine Sodium alginate Cationic liposome DOTAP Lysosomes escape Cancer Immunotherapy Toxicity 

分 类 号：R392[医药卫生—免疫学]