Nanoscale Zeolitic Imidazolate Framework-8 as Efficient Vehicles for Enhanced Delivery of CpG Oligodeoxynucleotides

CpG oligodeoxynucleotides (ODNs) activate the immune system and induce Th 1 responses by stimulation of Toll-like receptor 9 (TLR9). Thus, CpG ODNs have become immunotherapeutics against various diseases including cancers, allergies, and infection. However, applications of CpG ODNs are largely limited because of their easy degradation by DNase as well as inefficient cellular uptake. Development of efficient delivery systems capable of transferring CpG ODNs into immune cells is important to enhance their therapeutic efficacy. Herein, for the first time, we demonstrated the construction of a novel CpG ODNs delivery system by encapsulating CpG ODNs into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. ZIF-8 possessed high CpG ODNs loading capacity due to its porous structure. ZIF-8/CpG ODNs complexes exhibited good stability in a physiological environment but effectively released CpG ODNs in acid conditions corresponding to the TLR 9-localized endolysosomes. ZIF-8/CpG ODNs complexes had no cytotoxicity in contrast to ZIF-8. ZIF-8 significantly increased the intracellular uptake of CpG ODNs in RAW264.7 cells, which further enhanced the secretion of immune cytokines both in vitro and in vivo. Our results suggest that nanoscale metal-organic frameworks (MOFs) can serve as ideal vehicles for the delivery of CpG ODNs.