基于枸杞衍生碳点构建pH响应性纳米疫苗用于增强肿瘤免疫治疗OA

Immunotherapy has become a key focus in cancer treatment,and cancer nanovaccines have made significant progress as a representative approach in this field.However,some issues such as low immunogenicity,inefficient antigen delivery,and poor immune responses have limited the advancement of immunotherapy.To address these limitations,this study developed a pH-responsive nanovaccine(Lyc-OVA)based on Lycium barbarum-derived carbon dots(Lyc-CDs)synthesized via a green hydrothermal method.Owing to retained Lycium barbarum polysaccharides(LBP,18.43％total sugar content),Lyc-CDs demonstrated superior loading efficiency(48.40％)and pH-responsive release(80％OVA released within 24 h at pH 5.4)of OVA.Molecular docking simulations identified hydrogen bonding and π-cation interactions between LBP monosaccharides(rhamnose/galactose)and OVA.Lyc-OVA promoted dendritic cell maturation(32.87％CD80+CD86+cells,comparable to LPS)and cytokine secretion(TNF-α:13.10 pg mL-1;IFN-γ:17.78 pg mL-1;IL-6:3.74 pg mL-1).In a bilateral B16-OVA melanoma model,Lyc-OVA suppressed primary/distal tumor growth(80.36％/82.16％inhibition rates)by activating CD4+CD8+T cells,reducing immunosuppressive Treg/MDSC populations,and reshaping the tumor immune microenvironment.This work highlights the multifunctional role of natural polysaccharides in nanovaccine and provides an effective strategy for tumor immunotherapy.