Shanghai key laboratory of cell signaling and diseases, School of Life Science and Technology, Tongji University, Shanghai 200092, PR China.
Biomaterials. 2010 Feb;31(4):748-56. doi: 10.1016/j.biomaterials.2009.09.095. Epub 2009 Oct 23.
Layered double hydroxide (LDH) nanoparticles are attractive as potential drug vectors for the targeting not only of tissues, but also of intracellular organelles, and particularly the acidic endolysosomes created after cell endocytosis. The purpose of this study was to investigate the ability of LDH nanoparticles designed as vectors to activate dendritic cells (DCs), as measured by various cellular functions. The study also explored the possible signaling pathway through which the LDH nanoparticles exerted their effects on the cellular functions of DCs. First, LDH nanoparticles with different ratios of Mg(OH)(2) to Al(OH)(3) (1:1, 2:1 and 3:1, called R1, R2 and R3 respectively) were optimized and had a hydrodynamic diameter of 57 nm with a zeta potential of +35 mV. Then, the efficient endocytosis of the optimized LDH nanoparticles by bone marrow-derived dendritic cells (MDDCs) was monitored by fluorescence-activated cell sorting. The effect of R1, R2 and R3 on the expression of the pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined. The exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha, IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co-stimulatory molecules. Migration assays showed that R1 could increase the migration capacity of DCs to CCL21 and up-regulate the expression of CCR7. Furthermore, we found that R1 significantly increased the NF-kappaB expression in the nucleus (in a dose-dependent manner) and promoted the degradation of total IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might involve in an R1-induced DC activation. Our results suggested that LDH nanoparticles, in the future, may function as a useful vector for ex vivo engineering to promote vaccine delivery in immune cells.
层状双氢氧化物 (LDH) 纳米粒子作为潜在的药物载体具有吸引力，不仅可以靶向组织，还可以靶向细胞内细胞器，特别是细胞内吞作用后形成的酸性内溶酶体。本研究旨在探讨设计为载体的 LDH 纳米粒子激活树突状细胞 (DC) 的能力，方法是测量各种细胞功能。该研究还探讨了 LDH 纳米粒子对 DC 细胞功能发挥作用的可能信号通路。首先，优化了不同 Mg(OH)(2)/Al(OH)(3) 比例 (1:1、2:1 和 3:1，分别称为 R1、R2 和 R3) 的 LDH 纳米粒子，其水动力学直径为 57nm，表面电势为 +35mV。然后，通过荧光激活细胞分选监测优化后的 LDH 纳米粒子被骨髓来源的树突状细胞 (MDDC) 的有效内吞作用。研究了 R1、R2 和 R3 对 MDDC 中前炎症细胞因子 (TNF-α、IL-6 和 IL-12) 和共刺激分子 (CD40、CD80、CD86 和 MHC Ⅱ类) 表达的影响。结果表明，R1 的暴露会导致 TNF-α、IL-12、CD86 和 CD40 的表达呈剂量依赖性增加，而 R2 和 R3 不会上调这些细胞因子和共刺激分子。迁移实验表明，R1 可以增加 DC 对 CCL21 的迁移能力，并上调 CCR7 的表达。此外，我们发现 R1 可显著增加核内 NF-κB 表达 (呈剂量依赖性)，并促进总 IkappaBalpha 水平的降解，表明 NF-κB 信号通路可能参与 R1 诱导的 DC 激活。我们的研究结果表明，层状双氢氧化物纳米粒子将来可能作为一种有用的载体，用于体外工程以促进免疫细胞中的疫苗传递。
