Construction, characterization, and evaluation of nanosized curdlan sulfate/quaternary ammonium chitosan/CpG ODN...

CpG oligodeoxynucleotides (CpG ODNs), as nucleic acid adjuvants, effectively stimulate humoral and cellular immune responses. However, their clinical application is limited by drawbacks such as susceptibility to nuclease degradation and high negative charge, which impede cellular uptake. Previously, we have confirmed that polyelectrolyte complex nanoparticles composed of curdlan sulfate (CS) and O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/O-HTCC) could encapsulate negatively charged proteins and enhance their cellular internalization. Hence, in this study, CS/O-HTCC/CpG nanoparticles (C/O/CpG NPs) were prepared by electrostatic adsorption of positively charged CS/O-HTCC NPs with negatively charged CpG ODN and the formulation was optimized. Besides, the immunological activities of C/O/CpG NPs were evaluated both in vitro and in vivo. Moreover, their adjuvant properties and antitumor effects were assessed using ovalbumin (OVA) as a model antigen. The results showed that C/O/CpG NPs were uniformly spherical with a particle size and polydispersity index (PDI) of 119.67 ± 9.07 nm and 0.18 ± 0.01, respectively. C/O/CpG NPs stimulated the activation of antigen-presenting cells, induce antigen-specific cellular and humoral immune responses effectively and showed significant anti-tumor activity. In conclusion, C/O/CpG NPs could be considered as a promising class of adjuvants for tumor vaccines.