We present a facile strategy to fabricate nanovaccines through a metal–organic framework-templated method. The nanovaccines, named IMDQ@OVA-TA, were obtained through the interfacial assembly of model antigen ovalbumin (OVA) and tannic acid (TA) on imidazoquinoline (IMDQ)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs). The coordination of Zn²⁺-imidazole, Zn²⁺-TA, and the molecular coassembly of TA with proteins resulted in the formation of stable nanovaccines under physiological conditions. The pH responsiveness granted to the nanovaccines by coordination bonds promotes IMDQ release at low pH values, antigen lysosomal escape, and cross-presentation. In C57BL/6 mice models, nanovaccines demonstrated long-term accumulation at the injection site, sustainable transportation to lymph nodes, and good therapeutic effects against E.G7-OVA lymphoma. Mechanism analysis revealed that the nanovaccines induced both innate and adaptive tumor-specific immune activation. Overall, our work presents a simple and general strategy for the fabrication of protein-polyphenol nanocapsules with toll-like receptor (TLR) 7/8 agonists for cancer immunotherapy.

中文翻译：

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通过金属有机框架模板化疫苗纳米颗粒的纳米工程用于肿瘤免疫治疗


我们提出了一种通过金属有机框架模板方法制造纳米疫苗的简便策略。该纳米疫苗命名为IMDQ@OVA-TA，是通过模型抗原卵清蛋白（OVA）和单宁酸（TA）在咪唑喹啉（IMDQ）封装的沸石咪唑骨架8（ZIF-8）纳米颗粒（NP）上进行界面组装而获得的。 。 Zn ²⁺ -咪唑、Zn ²⁺ -TA 的配位以及 TA 与蛋白质的分子共组装导致在生理条件下形成稳定的纳米疫苗。通过配位键赋予纳米疫苗的 pH 响应性促进了 IMDQ 在低 pH 值下的释放、抗原溶酶体逃逸和交叉呈递。在C57BL/6小鼠模型中，纳米疫苗表现出在注射部位的长期积累、可持续运输至淋巴结以及对E.G7-OVA淋巴瘤的良好治疗效果。机制分析表明，纳米疫苗可诱导先天性和适应性肿瘤特异性免疫激活。总的来说，我们的工作提出了一种简单而通用的策略，用于制造具有 Toll 样受体 (TLR) 7/8 激动剂的蛋白质多酚纳米胶囊，用于癌症免疫治疗。