In vivo stepwise immunomodulation using chitosan nanoparticles as a platform nanotechnology for cancer immunotherapy
Dentritic cell (DC) based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH NP) based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic polycytidylic acid sodium salt (poly I:C) to target Toll like receptor 3 (TLR3) in endosomes. We developed CH NPs encapsulating ovalbumin (OVA) as a model antigen and poly I:C as the adjuvant in an ionic complex. These CH NPs showed increased in vivo intracellular delivery to the DCs in comparison with controls after injection into tumor bearing mice, and promoted DC maturation, leading to emergence of antigen specific cytotoxic CD8+ T cells. Finally, the CH NPs showed significantly greater antitumor efficacy in EG.7 and TC 1 tumor bearing mice compared to the control (p 0.01) Taken together, these data show that the CH NP platform can be used as an immune response modulatory vaccine for active cancer immunotherapy without ex vivo manipulation, thus resulting in increased anticancer efficacy.
Scientific reports