Magnetic nanoparticles enhance the cellular immune response of dendritic cell tumor vaccines by realizing the cytoplasmic delivery of tumor antigens

Dendritic cells (DCs)-based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment. However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe3O4@Ca/MnCO3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross-presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross-presentation of antigens. At the same time, the nanoparticles degradation product Mn2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca2+ ultimately promoted cellular immune response by increasing autophagy. The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8(+) T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines.