Construction and Antitumor Efficacy of an Antigen-Adjuvant Self-Carrier Spherical Peptide Nanovaccine.

Objective To construct a novel carrier-free nanovaccine to trigger a strong anti-tumor immune effect in the body. Methods The Toll-like receptor 4 agonist monophosphoryl lipid A （MPLA） was covalently conjugated with mucin 1 （MUC1）-targeting amino acid motif （Maa） to form MPLA-Maa monomer molecules.Subsequently，MPLA-Maa was self-assembled with Leu-His modified MUC1 polypeptide （LMP） to construct the nanovaccine system （MAP NVs）. Results MAP NVs exhibited a particle size of （169.85±4.05） nm，a polydispersity index of 0.308±0.021，and the Zeta potential of （-19.10±1.00） mV，and remained stable in vitro for over 10 days.Cell experiments showed that the nanovaccine significantly promoted dendritic cell maturation and activation and promoted tumor necrosis factor-α secretion.In the B16-MUC1 melanoma model，MAP NVs demonstrated remarkable antitumor effects，significantly inhibiting tumor growth and prolonging the survival of tumor-bearing mice.Mechanism analysis further revealed that MAP NVs effectively activated T cell immune response，promoted the proliferation of CD4+ and CD8+ T cells，and induced the production of CD8+ central memory T cells.After antigen restimulation，the secretion levels of tumor necrosis factor-α and interferon-γ were significantly elevated，which indicated long-lasting immune memory. Conclusions A carrier-free spherical peptide nanovaccine based on the co-delivery strategy of MPLA and LMP was successfully constructed.By promoting dendritic cell activation and enhancing T cell immune response，this system exhibits significant antitumor activity and long-lasting immune memory effect.This study provides a new technical approach and an experimental basis for developing nanovaccines against tumors.