An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO- Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-gamma secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy. (c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The rise of nanotechnology has brought new possibilities for cancer immunotherapy. However, most nanovaccines made with nanomaterials face challenges such as low drug load, unpredictable metabolism, and potential toxicity, which hinder their clinical applications. In this study, a self-assembled nanovaccine was developed using a modified antigen. It incorporated a mannose monomer that targets dendritic cells and a mevalonate pathway inhibitor called zoledronic acid (Zol) to enhance immune response. The nanovaccine demonstrated successful transport to lymph nodes, high internalization by dendritic cells, increased expression of costimulatory molecules, and effective antigen presentation. These superior properties led to significantly higher levels of serum antibodies, stronger cytotoxic T lymphocyte responses, and increased secretion of IFN-gamma compared to free antigen and adjuvants. In vivo experiments showed that the nanovaccine suppressed tumor growth and prolonged the survival of mice with EG7-OVA tumors. These findings suggest that our self-assembled nanovaccine holds promise for immune potentiation and cancer immunotherapy.