CpG oligodeoxynucleotides (CpG ODNs) are short single-stranded DNA molecules that are powerful in defeating diseases by inducing innate and adaptive immune response. Although there is ample evidence supporting the stimulatory effect of CpG ODNs, this activity is often transient due to the high susceptibility to serum nuclease degradation, poor targeting capacity, and inefficient cellular uptake. In this research, novel chitosan nanoparticles have been designed for encapsulation and delivery of CpG ODNs. The nanoparticles were assembled only using deionized water at room temperature, which is beneficial for maintaining CpG ODNs’ chemical structure and properties. The obtained nanoparticles were homogeneously dispersed with a mean size around 200 nm. The nanoparticles exhibited high CpG ODNs encapsulation efficiency and remained stable in storage under room temperature. The <i>in vitro</i> study using Raw 264.7 cells suggested that the nanoparticles were safe based on cell viability data and could efficiently deliver CpG ODNs into living cells and significantly increased the immunostimulatory activity. Raw 264.7 cells treated with nanocapsules also demonstrated a substantial upregulation of both TNF-a and IL-6 cytokines. Overall, these findings support the application of chitosan-based nanoparticles as vectors for the intracellular delivery of CpG ODNs for human and animal health.

Chitosan based nanoparticles for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides

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ACS Fall 2022

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