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pH-Responsive Biomimetic Polymeric Micelles as Lymph Node-Targeting Vaccines for Enhanced Antitumor Immune Responses.
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-06-04 , DOI: 10.1021/acs.biomac.0c00518 Xiqin Yang 1 , Tong Yu 1 , Yingping Zeng 1 , Keke Lian 1 , Xueqing Zhou 1 , Jia Ke 1 , Yinghong Li 2 , Hong Yuan 1 , Fuqiang Hu 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-06-04 , DOI: 10.1021/acs.biomac.0c00518 Xiqin Yang 1 , Tong Yu 1 , Yingping Zeng 1 , Keke Lian 1 , Xueqing Zhou 1 , Jia Ke 1 , Yinghong Li 2 , Hong Yuan 1 , Fuqiang Hu 1
Affiliation
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Lymph nodes are proposed as the intriguing target in cancer immunotherapy, and cellular immunity is vital for vaccines to fight against cancer. However, inefficient delivery of vaccines to lymph nodes and deficient lysosomal escape of antigens result in weak cellular immunity, which restrains the strength of vaccines in inducing antitumor immune responses. Hence, dendritic cell membrane (DCM)/histidine-modified stearic acid-grafted chitosan (HCtSA)/ovalbumin (OVA) micelles, as pH-responsive biomimetic vaccines, were fabricated to target lymph nodes and induce cellular immunity for enhanced antitumor immune responses. DCM/HCtSA/OVA micelles exhibited pH-dependent antigen release behavior, which resulted in efficient escape of antigens from dendritic cell (DC) lysosomes. Besides, DCM/HCtSA/OVA micelles accumulated and reserved in the lymph nodes, which ensured effective uptake by DCs. Importantly, DCM/HCtSA/OVA micelles induced potent T cell immune responses, promoted secretion of antitumor-related cytokines, and notably inhibited tumor growth. Overall, DCM/HCtSA/OVA micelles exhibit great potential in targeted immunotherapy and can provide guidance for the design of vaccines.
中文翻译：
pH响应仿生聚合物胶束作为淋巴结靶向疫苗，可增强抗肿瘤免疫反应。
淋巴结被提出作为癌症免疫治疗中引人入胜的目标，而细胞免疫对于疫苗抗癌至关重要。然而，疫苗到淋巴结的无效递送和抗原的溶酶体逸出不足导致细胞免疫力弱，这限制了疫苗诱导抗肿瘤免疫反应的强度。因此，制备了树突状细胞膜（DCM）/组氨酸修饰的硬脂酸接枝的壳聚糖（HCtSA）/卵清蛋白（OVA）胶束，作为pH响应仿生疫苗，以靶向淋巴结并诱导细胞免疫以增强抗肿瘤免疫应答。DCM / HCtSA / OVA胶束表现出pH依赖性的抗原释放行为，从而导致抗原从树突状细胞（DC）溶酶体中有效逸出。此外，DCM / HCtSA / OVA胶束积聚并保留在淋巴结中，这确保了DC的有效吸收。重要的是，DCM / HCtSA / OVA胶束可诱导强力的T细胞免疫反应，促进抗肿瘤相关细胞因子的分泌，并显着抑制肿瘤的生长。总体而言，DCM / HCtSA / OVA胶束在靶向免疫治疗中具有巨大潜力，可为疫苗设计提供指导。
更新日期：2020-07-13
中文翻译：
pH响应仿生聚合物胶束作为淋巴结靶向疫苗，可增强抗肿瘤免疫反应。
淋巴结被提出作为癌症免疫治疗中引人入胜的目标，而细胞免疫对于疫苗抗癌至关重要。然而，疫苗到淋巴结的无效递送和抗原的溶酶体逸出不足导致细胞免疫力弱，这限制了疫苗诱导抗肿瘤免疫反应的强度。因此，制备了树突状细胞膜（DCM）/组氨酸修饰的硬脂酸接枝的壳聚糖（HCtSA）/卵清蛋白（OVA）胶束，作为pH响应仿生疫苗，以靶向淋巴结并诱导细胞免疫以增强抗肿瘤免疫应答。DCM / HCtSA / OVA胶束表现出pH依赖性的抗原释放行为，从而导致抗原从树突状细胞（DC）溶酶体中有效逸出。此外，DCM / HCtSA / OVA胶束积聚并保留在淋巴结中，这确保了DC的有效吸收。重要的是，DCM / HCtSA / OVA胶束可诱导强力的T细胞免疫反应，促进抗肿瘤相关细胞因子的分泌，并显着抑制肿瘤的生长。总体而言，DCM / HCtSA / OVA胶束在靶向免疫治疗中具有巨大潜力，可为疫苗设计提供指导。
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