Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Engineering Research Center of Pharmaceutical Process Chemistry, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Int J Pharm. 2023 May 10;638:122914. doi: 10.1016/j.ijpharm.2023.122914. Epub 2023 Apr 5.
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.
胆固醇（CHOL）对于开发用于基因传递的脂质纳米颗粒（LNPs）至关重要，因为它可以增强膜融合并提高基因货物的传递效率。通过用在 LNPs 中取代 CHOL 的熊果酸（CA）修饰的脂质纳米颗粒（CLNPs）来开发有吸引力的 pDNA 载体，以各种氮基团与磷酸基团的比例（N/P）传递 pDNA。具有较高 CHOL/CA 比例的所得 CLNPs 表现出与 LNPs 相似的平均粒径、ζ电位和包封效率。与 LNPs 相比，CLNPs（CHOL:CA 比例=2:1）在保持低细胞毒性的同时，增加了细胞摄取并提高了转染功效。来自鸡实验的体内结果表明，与更高 N/P 比例的 LNPs 相比，用 N/P 比为 3 包封针对禽流感的 DNA 疫苗的 CLNPs 可以引起类似水平的体液和细胞免疫反应，从而表明使用较少可离子化脂质诱导理想的免疫效果。我们的研究为进一步研究 CA 在 LNPs 中的基因传递应用以及针对禽流感的新型 DNA 疫苗传递系统的开发提供了参考。
