Tianjin Key Laboratory of Biomaterial Research, Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Tianjin Key Laboratory of Biomaterial Research, Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Colloids Surf B Biointerfaces. 2021 Jan;197:111378. doi: 10.1016/j.colsurfb.2020.111378. Epub 2020 Sep 28.
Cancer immunotherapy is an important tumor therapy option for prevention and treatment of tumors and has attracted tremendous interests. However, the therapeutic outcomes are limited by insufficient antigen uptake and presentation by antigen-presenting cells such as dendritic cells (DCs). In this study, mannose-functionalized antigen nanoparticles with endosome escape activity were designed for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy. Mannose was selected as DCs targeting ligand to enhance antigen uptake. Model antigen ovalbumin (OVA) was directly conjugated with mannose to obtain DCs targeting antigen, which was then complexed with polyethylenimine (PEI) through electrostatic interaction to form mannose-functionalized antigen nanoparticles (MAN-OVA/PEI NPs). Flow cytometry analysis revealed that the MAN-OVA/PEI NPs greatly increased antigen uptake by DCs compared with OVA/PEI NPs. Confocal laser scanning microscopy further demonstrated that MAN-OVA/PEI NPs enhanced cytosolic antigen release. Moreover, MAN-OVA/PEI NPs significantly promoted cytokine production and DCs maturation in vitro. More importantly, MAN-OVA/PEI NPs treated DCs exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro. This work suggests that mannose-functionalized antigen nanoparticles provide a versatile delivery vehicle for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy.
癌症免疫疗法是肿瘤预防和治疗的一种重要肿瘤治疗选择，引起了极大的关注。然而，治疗效果受到抗原呈递细胞（如树突状细胞（DCs））摄取和呈递抗原不足的限制。在这项研究中，设计了具有内体逃逸活性的甘露糖功能化抗原纳米颗粒，用于靶向 DCs，加速内体逃逸并增强 MHC-I 抗原呈递，用于癌症免疫治疗。选择甘露糖作为 DCs 的靶向配体以增强抗原摄取。模型抗原卵清蛋白（OVA）与甘露糖直接缀合以获得靶向 DC 的抗原，然后通过静电相互作用与聚乙烯亚胺（PEI）复合形成甘露糖功能化抗原纳米颗粒（MAN-OVA/PEI NPs）。流式细胞术分析表明，与 OVA/PEI NPs 相比，MAN-OVA/PEI NPs 大大增加了 DCs 对抗原的摄取。共聚焦激光扫描显微镜进一步证实，MAN-OVA/PEI NPs 增强了细胞质中抗原的释放。此外，MAN-OVA/PEI NPs 显著促进了细胞因子的产生和 DCs 的体外成熟。更重要的是，MAN-OVA/PEI NPs 处理的 DCs 在体外对 B3Z T 细胞杂交瘤表现出增强的交叉呈递作用。这项工作表明，甘露糖功能化抗原纳米颗粒为靶向 DCs、加速内体逃逸和增强 MHC-I 抗原呈递提供了一种通用的递药载体，用于癌症免疫治疗。
