物理化学学报 >> 2026, Vol. 42 >> Issue (6): 100203.doi: 10.1016/j.actphy.2025.100203

所属专题: 碳点功能材料

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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

徐庆文1, 谢志刚2,*(), 郑敏1,*()   

  1. 1 长春工业大学化学与生命科学学院, 材料科学高等研究院, 吉林 长春 130012
    2 中国科学院长春应用化学研究所, 高分子生态材料重点实验室, 吉林 长春 130022
  • 收稿日期:2025-09-01 修回日期:2025-10-19 录用日期:2025-10-19 发布日期:2026-04-21
  • 通讯作者: Email: xiez@ciac.ac.cn (谢志刚)zhengm@ciac.ac.cn (郑敏)

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

Qingwen Xu1, Zhigang Xie2,*(), Min Zheng1,*()   

  1. 1 College of Chemistry and Life Sciences, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, Jilin Province, China
    2 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin Province, China
  • Received:2025-09-01 Revised:2025-10-19 Accepted:2025-10-19 Published:2026-04-21
  • Contact: Email: xiez@ciac.ac.cn (Zhigang Xie)zhengm@ciac.ac.cn (Min Zheng)

摘要:

免疫治疗已成癌症治疗的研究热点,癌症纳米疫苗作为该领域的代表性治疗方式取得了显著进展。然而,免疫原性低、抗原递送效率不足、免疫应答效果差等问题限制了免疫治疗的发展。为解决这些局限性,本研究通过绿色水热法合成枸杞衍生碳点(Lyc-CDs),并基于此开发了一种pH响应性纳米疫苗(Lyc-OVA)。由于保留了枸杞多糖(LBP,总含糖量18.43%),Lyc-CDs对卵清蛋白(OVA)表现出优异的负载效率(48.40%)和pH响应释放特性(在pH 5.4条件下,OVA在24 h内的释放率为80%)。分子对接模拟表明,LBP单糖(鼠李糖/半乳糖)与OVA之间存在氢键和π-阳离子相互作用。Lyc-OVA可促进树突状细胞成熟(CD80⁺CD86⁺占比32.87%,与脂多糖(LPS)相当)并诱导细胞因子分泌(肿瘤坏死因子-α (TNF-α):13.10 pg mL−1;干扰素-γ (IFN-γ):17.78 pg mL−1;白细胞介素-6 (IL-6):3.74 pg mL−1)。在双侧B16-OVA黑色素瘤模型中,Lyc-OVA通过激活CD4+CD8+T细胞、减少免疫抑制性调节性T细胞(Treg)/髓系来源抑制细胞(MDSC)群体及重塑肿瘤免疫微环境,抑制原发/远端肿瘤生长(抑制率分别为80.36%/82.16%)。本研究揭示了天然多糖在纳米疫苗中的多功能作用,为肿瘤免疫治疗提供了有效策略。

关键词: 枸杞, 碳点, 纳米疫苗, 肿瘤微环境, 肿瘤免疫治疗

Abstract:

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.

Key words: Lycium barbarum, Carbon dots, Nanovaccines, Tumor microenvironment, Tumor immunotherapy