MnO₂nanoparticles as a minimalist multimode vaccine adjuvant/delivery system to regulate antigen presenting cells for tumor immunotherapy

In the field of tumor immunotherapy, tumor vaccines have unique advantages including fewer side effects, tumor-specificity and immune memory, and hence attract more and more attention. In the development of tumor vaccines, a critical challenge lies in the exploitation of appropriate vaccine adjuvants/delivery systems that need to meet multiple requirements to achieve potent cellular immunity while simultaneously requiring single composition to simplify the clinical translation process. Among numerous materials, only manganese dioxide (MnO2) nanoparticles with rare physicochemical properties seem to meet the demanding criteria of simplicity and multifunctionality. However, the potential of MnO2 nanoparticles as vaccine adjuvants/delivery systems has not been well exploited, despite their widespread applications in the biomedical field. In this study, the mechanism and efficacy of single MnO2 nanoparticles as a minimalist multi-mode tumor vaccine adjuvant/delivery system were fully investigated by using a model antigen ovalbumin (OVA) to construct tumor vaccines OVA/MnO2. The obtained results show that MnO2 nanoparticles act as an ideal delivery system by multiple modes to deliver the antigen to the cytoplasm of dendritic cells to induce cellular immune response. Moreover, MnO2 nanoparticles also act as a superior adjuvant depot to sustainably release Mn2+ to enhance the immune response through a STING pathway in dendritic cells. Both the delivery function and the adjuvant effect of MnO2 nanoparticles contribute to improved cellular immunity and anti-tumor efficacy of tumor vaccines OVA/MnO2. From the results, MnO2 nanoparticles are found to be a promising minimalist multi-mode vaccine adjuvant/delivery system for the development of practical tumor vaccines.