Tenth People's Hospital, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
Biomaterials. 2014 Jan;35(1):466-78. doi: 10.1016/j.biomaterials.2013.09.060. Epub 2013 Oct 4.
Various approaches have been used to improve systemic immune response to infectious disease or virus, and DNA vaccination has been demonstrated to be one of these effective ways to elicit protective immunity against pathogens. Our previous studies showed that layered double hydroxides (LDH) nanoparticles could be efficiently taken up by the MDDCs and had an adjuvant activity for DC maturation. To further enhance the immune adjuvant activity of LDH, core-shell structure SiO2@LDH nanoparticles were synthesized with an average diameter of about 210 nm. And its high transfection efficiency in vitro was demonstrated by using GFP expression plasmid as model DNA. Exposing SiO2@LDH nanoparticles to macrophages caused a higher dose-dependent expression of IFN-γ, IL-6, CD86 and MHC II, compared with SiO2 and LDH respectively. Furthermore, in vivo immunization of BALB/c mice indicated that, DNA vaccine loaded-SiO2@LDH nanoparticles not only induced much higher serum antibody response than naked DNA vaccine and plain nanoparticles, but also obviously promoted T-cell proliferation and skewed T helper to Th1 polarization. Additionally, it was proved that the caveolae-mediated uptake of SiO2@LDH nanoparticles by macrophage lead to macrophages activation via NF-κB signaling pathway. Our results indicate that SiO2@LDH nanoparticles could serve as a potential non-viral gene delivery system.
已经有多种方法被用于提高机体对传染病或病毒的全身免疫反应，而 DNA 疫苗已被证明是一种有效的方法，可以激发针对病原体的保护性免疫。我们之前的研究表明，层状双氢氧化物（LDH）纳米颗粒可以被 MDDC 高效摄取，并具有促进 DC 成熟的佐剂活性。为了进一步增强 LDH 的免疫佐剂活性，我们合成了具有约 210nm 平均直径的核壳结构的 SiO2@LDH 纳米颗粒。并且通过使用 GFP 表达质粒作为模型 DNA，证明了其在体外的高转染效率。将 SiO2@LDH 纳米颗粒暴露于巨噬细胞中会引起更高剂量依赖性的 IFN-γ、IL-6、CD86 和 MHC II 的表达，与 SiO2 和 LDH 相比分别。此外，体内免疫 BALB/c 小鼠表明，负载-SiO2@LDH 纳米颗粒的 DNA 疫苗不仅诱导比裸 DNA 疫苗和普通纳米颗粒更高的血清抗体反应，而且明显促进 T 细胞增殖，并使 T 辅助细胞向 Th1 极化倾斜。此外，已经证明巨噬细胞通过 caveolae 介导的 SiO2@LDH 纳米颗粒摄取导致巨噬细胞通过 NF-κB 信号通路被激活。我们的结果表明，SiO2@LDH 纳米颗粒可以作为一种潜在的非病毒基因传递系统。
