Signalling pathways involved in the activation of dendritic cells by layered double hydroxide nanoparticles.
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.
Shanghai key laboratory of cell signaling and diseases, School of Life Science and Technology, Tongji University, Shanghai 200092, PR China.
Ang
A
Li
Lili
L
Qin
Di
D
Zhu
Rongrong
R
Zhu
Jing
J
Sun
Shilong
S
Wang
D000536:Aluminum Hydroxide / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D006878:Hydroxides / Q000737:chemistry* / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008276:Magnesium Hydroxide / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D006878:Hydroxides; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000536:Aluminum Hydroxide; C031356:hydroxide ion; D008276:Magnesium Hydroxide