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  3. A structurally distinct arabinose-bridged arabinogalactan from Lycium barbarum as a TLR4-activating adjuvant for nanovaccine-based cancer immunotherapy

A structurally distinct arabinose-bridged arabinogalactan from Lycium barbarum as a TLR4-activating adjuvant for nanovaccine-based cancer immunotherapy

  • Carbohydr Polym. 2026 Feb 1:373:124618. doi: 10.1016/j.carbpol.2025.124618.
Chun-Jie Bao 1,  Meng-Qiu Liu 2,  Ya-Nan Liu 3,  Li-Qiang Zhao 3,  Yu-Xuan Li 3,  Xin-Lan Zhang 3,  Fang Zhang 3,  Sheng Guo 3,  Er-Xin Shang 3,  Jia-Lun Duan 4,  Jin-Ao Duan 5
Affiliations

Affiliations

  • 1 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Provincial Key Laboratory of Functional Substances in Traditional Chinese Medicine Formulae and Innovative Drug Discovery, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 2 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Provincial Key Laboratory of Functional Substances in Traditional Chinese Medicine Formulae and Innovative Drug Discovery, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Suzhou Hospital of Xiyuan Hospital of China Academy of Chinese Medical Science, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215000, China.
  • 3 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Provincial Key Laboratory of Functional Substances in Traditional Chinese Medicine Formulae and Innovative Drug Discovery, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 4 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Provincial Key Laboratory of Functional Substances in Traditional Chinese Medicine Formulae and Innovative Drug Discovery, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
  • 5 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Provincial Key Laboratory of Functional Substances in Traditional Chinese Medicine Formulae and Innovative Drug Discovery, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
PMID: 41320397 DOI: 10.1016/j.carbpol.2025.124618
Abstract

Current studies on plant-derived adjuvants focus on heterogeneous or partially characterized Polysaccharides, while the adjuvanticity of structurally defined, arabinogalactan (AG)-rich polysaccharide in Cancer nanovaccine settings remains unexplored. Here, we identify and characterize NLBPE1, a homogeneous AG-rich polysaccharide isolated from Lycium barbarum, which features an atypical arabinose-bridged structure. Unlike canonical AG-I or AG-II motifs, NLBPE1 contains galactose side chains connected to the rhamnogalacturonan backbone via → 5)-α-Araf-(1 → linkages, forming a structurally distinct AG topology. Mechanistic studies demonstrate that NLBPE1 activates dendritic cells through the TLR4-IKK-NF-κB signaling axis, promoting antigen uptake, cross-presentation, and proinflammatory cytokine release. When co-formulated in a PLGA-based nanovaccine with a model antigen, NLBPE1 markedly enhances CD8+ T cell priming, leading to effective tumor control in vivo. Moreover, combination with anti-PD-1 immune checkpoint blockade yields synergistic antitumor responses in a melanoma model. Together, these findings establish NLBPE1 as a structurally and mechanistically distinct polysaccharide Adjuvant with translational potential for next-generation Cancer nanovaccine strategies.

Keywords

Arabinogalactan; Cancer immunotherapy; Lycium barbarum polysaccharide; Nanovaccine adjuvant; TLR4 activation.

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