Nanomaterial-assisted delivery of CpG oligodeoxynucleotides for boosting cancer immunotherapy

Cancer immunotherapy aims to improve immunity to not only eliminate the primary tumor but also inhibit metastasis and recurrence. It is considered an extremely promising therapeutic approach that breaks free from the traditional paradigm of oncological treatment. As the medical community learns more about the immune system's mechanisms that “turn off the brake” and “step on the throttle”, there is increasingly successful research on immunomodulators. However, there are still more restrictions than countermeasures with immunotherapy related to immunomodulators, such as low responsiveness and immune-related adverse events that cause multiple adverse reactions. Therefore, medical experts and materials scientists attempted to the efficacy of immunomodulatory treatments through various methods, especially nanomaterial-assisted strategies. CpG oligodeoxynucleotides (CpG) not only act as an adjuvant to promote immune responses, but also induce autophagy. In this review, the enhancement of immunotherapy using nanomaterial-based CpG formulations is systematically elaborated, with a focus on the delivery, protection, synergistic promotion of CpG efficacy by nanomaterials, and selection of the timing of treatment. In addition, we also discuss and prospect the existing problems and future directions of research on nanomaterials in auxiliary CpG therapy.