Engineering a Nanoscale Al‐MOF‐Armored Antigen Carried by a “Trojan Horse”‐Like Platform for Oral Vaccination to Induce Potent and Long‐Lasting Immunity

Abstract

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 ioncontaining 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.

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“…Meanwhile, to develop the bilateral tumor model, we injected the cells into both left and right armpits of each mouse. When the tumor volume reached 75 mm 3 , the mice were used in the following experiments.…”

“…Mouse weight, primary tumor volume, and distant tumor volume were measured and recorded every day for 32 days. When the size of the tumor exceeded 1,000 mm 3 , euthanasia was carried out according to animal care protocols.…”

“…In brief, total protein (100 mg) and specific caspase-3, -8, and -9 substrate enzymes (5 mL) were added to the 96-well plate and incubated for 2 h at 37 C. Caspase activities were determined by using a fluorometric method with the emission and excitation wavelengths set at 380 nm and 440 nm, respectively. 31 Biodistribution Analysis in Normal and Tumor Tissues Female BALB/c nude mice with A375 tumor size of 75 mm 3 were selected and injected with GTe and GTe-RGD at concentrations of 1 mg/kg (Te concentration, injection volume 0.2 mL) intravenously. Three 3 days after injection these mice were executed and the major tissues including heart, liver, spleen, liver, kidney, and tumor ll…”

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