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首页> 外文期刊>Advanced Functional Materials >Engineering a Nanoscale Al-MOF-Armored Antigen Carried by a 'Trojan Horse'-Like Platform for Oral Vaccination to Induce Potent and Long-Lasting Immunity
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Engineering a Nanoscale Al-MOF-Armored Antigen Carried by a 'Trojan Horse'-Like Platform for Oral Vaccination to Induce Potent and Long-Lasting Immunity

机译：工程化由“特洛伊木马”之类的平台携带的纳米Al-MOF装甲抗原，用于口服疫苗以诱导强效和持久的免疫力。

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摘要

Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum-based metal-organic framework (Al-MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast-derived capsule is used to carry the Al-MOF-armored OVA as a "Trojan Horse"-like transport platform. In vitro experiments reveal that the mineralization of Al-MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al-MOFs can gradually disintegrate in a phosphate ion-containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the "Trojan Horse"-like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al-MOF-armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long-lasting, high-levels of mucosal S-IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.
机译：通过口服施用抗原进行疫苗接种面临许多挑战，包括胃肠道（GI）蛋白水解和粘膜屏障。为了限制GI蛋白水解，在环境抗原和卵清蛋白（OVA）模型上合成了仿生矿化的铝基金属-有机骨架（Al-MOF）系统，该系统具有抗环境温度和pH值的特性，并且可以协同用作递送载体。充当装甲。为了克服粘膜屏障，使用酵母衍生的胶囊来携带Al-MOF装甲的OVA作为“特洛伊木马”之类的运输平台。体外实验表明，Al-MOF的矿化作用在OVA上形成了盔甲，可以保护其免受高酸性和降解性GI条件的侵害。但是，矿化的Al-MOF可以在含磷酸根离子的模拟细胞内液中逐渐崩解，从而缓慢释放其封装的OVA。体内研究表明，“特洛伊木马”样运输平台专门针对肠道M细胞，有利于Al-MOF装甲的OVA的上皮运输，随后在局部巨噬细胞中发生内吞作用，最终在肠系膜淋巴结中蓄积，产生长持久的高水平粘膜S-IgA和血清IgG抗体。这样的工程递送平台可以代表用于预防性或治疗性抗原的口服施用以用于疫苗接种的有前途的策略。

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