Binding of CpG oligodeoxynucleotides to mesoporous silica nanoparticles for enhancing delivery efficiency

• A potential CpG delivery system was developed by binding of CpG onto aminated MSNs.
• CpG/MSN-NH2 complexes exhibited enhanced serum stability.
• CpG/MSN-NH2 complexes induced significantly high level of IL-6 production.

We developed a potential cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) delivery system by binding of CpG ODN onto aminated mesoporous silica nanoparticles (MSNs) to form CpG/MSN-NH2 complexes for Toll-like receptor 9 (TLR9)-mediated induction of cytokines. Serum stability, in vitro cytotoxicity, cellular uptake, and interleukin-6 (IL-6) induction of CpG/MSN-NH2 complexes were investigated. The results showed that MSN-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and binding of CpG ODN to MSN-NH2 nanoparticles enhanced serum stability of CpG ODN due to the protection by nanoparticles. Furthermore, CpG/MSN-NH2 complexes could be efficiently taken up by cells due to small particle size and good dispersity. Most importantly, CpG/MSN-NH2 complexes significantly enhanced the level of IL-6 induction, stimulated by interaction between CpG ODN and TLR9 in endolysosomes. Therefore, MSNs would be a promising carrier for enhancing the delivery efficiency of CpG ODN.

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