Magnetic mesoporous silica nanoparticles for CpG delivery to enhance cytokine induction via toll-like receptor 9

We developed a potential cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) delivery system based on magnetic mesoporous silica (MMS) nanoparticles by binding of CpG ODN onto aminated MMS (MMS-NH2) nanoparticles to form CpG/MMS-NH2 complexes for toll-like receptor 9 (TLR9)-mediated induction of cytokines. Magnetization, serum stability, in vitro cytotoxicity, cellular uptake, and interleukin-6 (IL-6) induction of CpG/MMS-NH2 complexes were evaluated. The results showed that MMS nanoparticles exhibited superparamagnetic behavior with a saturation magnetization of 6.5 emu g(-1). Also, MMS-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and CpG/MMS-NH2 complexes enhanced the serum stability of CpG ODN and could be localized in the endolysosomes after endocytosis by cells. Importantly, CpG/MMS-NH2 complexes significantly enhanced the TLR9-mediated IL-6 induction compared to free CpG ODN. Therefore, CpG/MMS-NH2 complexes could exhibit magnetic targeted delivery and significantly enhance the TLR9-mediated cytokine induction for stimulating immune responses.