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Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines

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Abstract

The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.19 kD; APSHMw, 135.67 kD) from Radix Astragali and made them self-assemble with OVA257−264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method. The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability. APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy. The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution. The FITC-OVA in APS-NVs could be effectively taken up by DCs, and APS-NVs could stimulate the maturation of DCs, improving the antigen cross-presentation efficiency in vitro. The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4. Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c. injection. Smaller APS-NVs could easily access the lymph nodes. Furthermore, APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells. In addition, APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group. The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region. Subsequently, the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs. Therefore, this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

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Acknowledgement

This work was supported by Key Project at Central Government Level: the ability establishment of sustainable use for valuable Chinese medicine resources (2060302-2305-04), CAMS Innovation Fund for Medical Sciences (2021-1-I2M-031, 2022-I2M-1-018, 2022-I2M-2-002), Jilin Provincial Fiscal Construction Program for High-Tech Industries and Technologies (2022C041-5, 20220401117YY), Hohhot Science and Technology Program (2021-Social-4).

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  1. Contributed equally to this work

Authors and Affiliations

  1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS), Institute of Medicinal Plant Development (IMPLAD), Beijing, 100193, China

    Nan Li, Yun Zhang, Tian Liu, Xiaobo Sun & Zhengqi Dong

  2. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine from Ministry of Education, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription from Chinese Academy of Medical Sciences, CAMS, IMPLAD, Beijing, 100193, China

    Nan Li, Yun Zhang, Tian Liu, Yikai Fan, Fan Ye, Guibo Sun, Xiaobo Sun & Zhengqi Dong

  3. Department of Pharmaceutics, School of Pharmaceutical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150036, China

    Miaomiao Han, Jinjia Wu, Yingxia Xiong & Bing Jin

  4. Jilin Academy of Chinese Medicine Sciences, Changchun, 130012, China

    Yun Zhang & Yinghua Zhang

  5. Joint Research Center for Chinese Medicinal Herbs, IMPLAD, ABRC & ACCL, Beijing, 100193, China

    Xiaobo Sun & Zhengqi Dong

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  1. Nan Li
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  2. Yun Zhang
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Correspondence to Xiaobo Sun or Zhengqi Dong.

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The author(s) declare that they have no conflict of interest. All animal procedures were approved by the Institutional Animal Care and Use Committee at the Institute of Medicinal Plant Development (ethical approval No. SLXD-20230905013; Date of ethical approval: September 6, 2023) and performed in accordance with the EU Directive 2010/63/EU for animal experiments.

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Li, N., Zhang, Y., Han, M. et al. Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines. Sci. China Life Sci. 67, 680–697 (2024). https://doi.org/10.1007/s11427-023-2465-x

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