Construction of pH-responsive Lycium barbarum-derived carbon dots nanovaccines for enhanced anti-tumor immunotherapy

Recent advancements in cancer vaccine development have demonstrated their potential for precise tumor targeting through antigen-specific immune activation. Nevertheless, critical challenges persist in clinical translation, including inefficient antigen cross-presentation, suboptimal carrier-mediated immunogenicity, and systemic immune-related adverse events. These drawbacks highlight the pressing requirement for creative approaches to engineer next-generation vaccine platforms that synergistically enhance antigen delivery efficiency, immune activation precision, and biosafety.

Herein, this study constructed a pH-responsive nanovaccine (Lyc-OVA) based on polysaccharide-functionalized CDs derived from Lycium barbarum (Lyc-CDs). The unique surface chemistry of Lyc-CDs, enriched with hydroxyl/amino groups and retained LBP, endowed Lyc-OVA with high antigen-loading capacity (48.4%) and tumor microenvironment-triggered release (80% OVA release at pH 5.4). In vitro, Lyc-OVA enhanced DCs maturation (CD80⁺CD86⁺ proportion matching LPS controls) and pro-inflammatory cytokine secretion (TNF-α, IFN-γ and IL-6). In vivo, Lyc-OVA significantly inhibited primary/distal tumor growth (80.36%/82.16% inhibition rates) by activation of CD4⁺CD8⁺ T cells，reduction of immunosuppressive Treg/MDSC populations and reprogramming of the tumor immune microenvironment.