文献类型：期刊文献

英文题名：Corosolic acid-modified lipid nanoparticles as delivery carriers for DNA vaccines against avian influenza

作者：Guo, Ziyan[1];Jing, Qiufang[2];Xu, Zhongyu[2];Zhang, Dahe[3];Zheng, Wenyun[4];Ren, Fuzheng[1,2,4]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Suzhou Womei Biol Co Ltd, Suzhou 215613, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：638

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000980652900001)】；

基金：Acknowledgement This work was supported by Shanghai Key Laboratory of New Drug Design (Grant No. 17DZ2271000) , and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：Lipid nanoparticles; Cholesterol; Corosolic acid; Avian influenza vaccine; Immune responses

摘要：Cholesterol (CHOL) is essential for developing lipid nanoparticles (LNPs) for gene delivery because it enhances membrane fusion and improves the delivery efficiency of gene cargos. An attractive pDNA carrier, corosolic acid (CA)-modified lipid nanoparticles (CLNPs), was developed by replacing CHOL in LNPs to deliver pDNA at various ratios of nitrogen groups to phosphate groups (N/P). The resultant CLNPs with a higher CHOL/CA ratio exhibited similar mean particle size, zeta potential, and encapsulation efficiency to those of LNPs. In comparison with LNPs, CLNPs (CHOL:CA ratio = 2:1) achieved increased cellular uptake and enhanced transfection efficacy while maintaining low cytotoxicity. In vivo results from chicken experiments demonstrated that CLNPs encapsulating DNA vaccines against avian influenza at a N/P ratio of 3 could elicit similar-level humoral and cellular immune responses compared with those of LNPs at a higher N/P ratio, thereby suggesting the induction of desirable immune effects using less ionizable lipids. Our study provides a reference for further research on the application of CA in LNPs for gene delivery, and the development of novel delivery systems for DNA vaccines against avian influenza.