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

Abstract

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.