Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Nanotechnology. 2013 Jul 26;24(29):295101. doi: 10.1088/0957-4484/24/29/295101. Epub 2013 Jun 25.
To construct mannosylated liposomes/protamine/DNA (LPD) carriers for DNA vaccine targeting to dendritic cells (DCs), a mannosylated cholesterol derivative (Man-C6-Chol) was synthesized via simple ester linkage and amide bonds. Then, the Man-C6-Chol was applied to LPD formulation as a synthetic ligand. The physicochemical properties of mannosylated LPD (Man-LPD) were first evaluated, including the size and zeta potential, morphology and the ability to protect DNA against DNase I degradation. Man-LPD showed a small size with a stable viral-like structure. In comparison to non-mannose liposomes/LPD (Man-free liposomes/LPD), mannosylated liposomes/LPD (Man-liposomes/Man-LPD) exhibited higher efficiency in both intracellular uptake (2.3-fold) and transfection (4.5-fold) in vitro. Subsequent MTT assays indicated that the LPD carriers had low toxicity on the tested cells. Afterwards, the investigation into the maturation activation on primary bone marrow-derived DCs (BMDCs) showed that both Man-LPD and Man-free LPD induced remarkable up-regulation of CD80, CD86 and CD40 on BMDCs. Inspired by these studies, we can conclude that the synthetic mannosylated LPD targeting to DCs was a potential carrier for DNA vaccine.
为构建靶向树突状细胞（DC）的 DNA 疫苗甘露糖化脂质体/鱼精蛋白/DNA（LPD）载体，通过简单的酯键和酰胺键合成了一种甘露糖胆固醇衍生物（Man-C6-Chol）。然后，将 Man-C6-Chol 作为合成配体应用于 LPD 制剂中。首先对甘露糖化 LPD（Man-LPD）的理化性质进行了评价，包括粒径和 Zeta 电位、形态和保护 DNA 免受 DNA 酶 I 降解的能力。Man-LPD 表现出较小的粒径和稳定的病毒样结构。与非甘露糖脂质体/LPD（无 Man 脂质体/LPD）相比，甘露糖化脂质体/LPD（Man-脂质体/Man-LPD）在体外具有更高的细胞内摄取效率（2.3 倍）和转染效率（4.5 倍）。随后的 MTT 分析表明，LPD 载体对测试细胞的毒性较低。随后，对原代骨髓来源的树突状细胞（BMDC）的成熟激活的研究表明，Man-LPD 和无 Man 脂质体都能显著上调 BMDC 上的 CD80、CD86 和 CD40。基于这些研究，我们可以得出结论，靶向 DC 的合成甘露糖化 LPD 是一种有潜力的 DNA 疫苗载体。
