Xu Jing, Luft J Christopher, Yi Xianwen, Tian Shaomin, Owens Gary, Wang Jin, Johnson Ashley, Berglund Peter, Smith Jonathan, Napier Mary E, DeSimone Joseph M
Department of Chemistry, △Department of Pharmacology, ∥UNC Eshelman School of Pharmacy, †Carolina Center of Cancer Nanotechnology Excellence, ⊥Institute for Advanced Materials, #Institute for Nanomedicine, ¶Lineberger Comprehensive Cancer Center, and ■Department of Biochemistry and Biophysics, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
Mol Pharm. 2013 Sep 3;10(9):3366-74. doi: 10.1021/mp400190z. Epub 2013 Aug 21.
Herein we report the development of a nonviral lipid-complexed PRINT (particle replication in nonwetting templates) protein particle system (LPP particle) for RNA replicon delivery with a view toward RNA replicon-based vaccination. Cylindrical bovine serum albumin (BSA) particles (diameter (d) 1 μm, height (h) 1 μm) loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology. Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that (1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines and (2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles.
在此，我们报告了一种用于RNA复制子递送的非病毒脂质复合PRINT（非湿润模板中的颗粒复制）蛋白颗粒系统（LPP颗粒）的开发，旨在用于基于RNA复制子的疫苗接种。使用PRINT技术制备了装载RNA复制子并用完全可逆的二硫键交联剂稳定的圆柱形牛血清白蛋白（BSA）颗粒（直径（d）1μm，高度（h）1μm）。通过将颗粒与1,2-二油酰基-3-三甲基铵丙烷（DOTAP）和1,2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE）脂质的混合物复合，实现了颗粒向Vero细胞的高效递送。我们的数据表明：（1）这种脂质复合蛋白颗粒是递送基于RNA复制子的疫苗的有前景的系统；（2）为了通过基于蛋白的颗粒成功递送RNA复制子，使用可降解的交联剂是必要的。
