We developed a potential cytosine−phosphodiester−guanine oligodeoxynucleotide (CpG ODN) delivery system combining amino-modified mesoporous silica SBA-15 (SBA-NH2) particles with polycation poly(allylamine hydrochloride) (PAH) to form SBA-ODN-PAH complexes. Stability, cell uptake, in vitro cytotoxicity, and the nuclear factor κB (NF-κB) activity of the SBA-ODN-PAH complexes were evaluated. Gel electrophoresis indicated that the SBA-ODN-PAH complexes exhibited enhanced serum stability due to the dual protection effects of the SBA-NH2 particles and the PAH coating. The SBA-ODN-PAH complexes were taken up by 293XL-hTLR9 cells and little cytotoxicity was expressed in a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Most importantly, the SBA-ODN-PAH complexes significantly enhanced NF-κB activity, stimulated by interaction between the internalized CpG ODN and Toll-like receptor 9, compared to free CpG ODN and SBA-ODN complexes. Thus, SBA-ODN-PAH complexes provide a promising strategy for e...