抗原-免疫佐剂自载体球形多肽纳米疫苗的构建与抗肿瘤效应OA

Objective To construct a novel carrier-free nanovaccine to trigger a strong anti-tumor im-mune effect in the body.Methods The Toll-like receptor 4 agonist monophosphoryl lipid A(MPLA)was cova-lently conjugated with mucin 1(MUC1)-targeting amino acid motif(Maa)to form MPLA-Maa monomer mole-cules.Subsequently,MPLA-Maa was self-assembled with Leu-His modified MUC1 polypeptide(LMP)to con-struct 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 matu-ration 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 re-sponse,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 pep-tide 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.