Nanodelivery systems for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides

Synthetic oligodeoxynucleotides containing immunostimulatory CpG motif mimic bacterial DNA and are potent activator of innate and adaptive immune responses. Therefore, CpG ODNs have significant potentials as immunotherapeutic agent for treatment of infectious diseases, allergy and cancer. Many clinical trials involving CpG ODNs either used alone or as adjuvant have been initiated. However, delivery of CpG ODNs to target sites still remains a great challenge due to their extreme susceptibility to nuclease degradation in serum and poor cellular uptake. Chemical modification of CpG ODNs backbone can protect them against degradation by nucleases, but have raised concern regarding several severe side effects. Development of efficient CpG ODNs delivery systems to address these issues and enhance their immunostimulatory effect are highly desirable. In recent years, the emergence of nanotechnology has provided unprecedented opportunities to encapsulate CpG ODN into various nanocarriers or synthesize CpG ODNs nanostructures. This review provides an overview of the delivery systems based on nanomaterials and nanostructures newly developed for enhancing the immunostimulatory effect of CpG ODNs, together with a brief discussion on perspectives for future studies in this field.