Cationic Starch Nanoparticles for Enhancing CpG Oligodeoxynucleotide-Mediated Antitumor Immunity

CpG ODNs demonstrate a significant promise for immunotherapy. However, their application is limited owing to quick DNase digestion and inadequate cellular internalization. Transportation of CpG ODNs into immune cells is crucial. Although viral vectors exhibit high transfection efficiency, safety risks, high cost, and low carrying capacity remain big obstacles. Herein, a novel CpG ODNs vector was fabricated by using starch. Starch was ultrasonicated and simply aminated (NH₂-St) through grafting with diethylenetriamine, which was spherical with a diameter of 50 nm. NH₂-St possessed good biocompatibility. Cationic NH₂-St encapsulated CpG ODNs well and possessed a high loading capacity of 317 μg/mg. NH₂-St protected CpG ODNs from nuclease digestion and significantly enhanced their cellular uptake. NH₂-St/CpG induced the potent secretion of antitumor cytokines from macrophages and effectively suppressed the growth of tumor cells. This work highlights the promise of starch for CpG ODNs delivery, which brings new hope for cancer immunotherapy.