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

作　　者：Nan Li Yun Zhang Miaomiao Han Tian Liu Jinjia Wu Yingxia Xiong Yikai Fan Fan Ye Bing Jin Yinghua Zhang Guibo Sun Xiaobo Sun Zhengqi Dong 

机构地区：[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 [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 [3]Department of Pharmaceutics,School of Pharmaceutical Sciences,Heilongjiang University of Chinese Medicine,Harbin 150036,China [4]Jilin Academy of Chinese Medicine Sciences,Changchun 130012,China [5]Joint Research Center for Chinese Medicinal Herbs,IMPLAD,ABRC&ACCL,Beijing 100193,China

出　　处：《Science China(Life Sciences)》2024年第4期680-697,共18页中国科学（生命科学英文版）

基　　金：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)。

摘　　要：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 k D;APSHMw,135.67 k D)from Radix Astragali and made them self-assemble with OVA257–264directly 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.

关 键 词：Astragalus polysaccharides nanovaccines OVA IMMUNOTHERAPY self-adjuvant 

分 类 号：R730.51[医药卫生—肿瘤]