Metal‐Organic‐Framework‐Based Vaccine Platforms for Enhanced Systemic Immune and Memory Response

Abstract

Nanoparticulate delivery platforms have shown promising advantages for vaccines in many aspects. However, their application was limited so far by lengthy synthetic protocols, the requirement of specific modification of antigen, and by the low efficiency in inducing antigen‐specific cytotoxic T‐lymphocyte responses. This study demonstrates for the first time the construction of metal‐organic‐framework (MOF) based vaccines by encapsulating ovalbumin (OVA) and attaching the cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) in/on zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles. The pH responsive decomposition feature enables the system to release the protein antigens and CpG ODNs in the same antigen presenting cells more efficiently. More importantly, in addition to the induction of a potent immune memory response, both in vitro and in vivo experiments show that the vaccines can induce strong humoral and cellular immunity. These findings suggest that the MOF‐based vaccine platforms can be used to produce effective vaccines against a range of ailments, which will facilitate the application of MOFs in biomedical areas.

A New Strategy to Reduce Toxicity of Ethidium Bromide by Alternating Anions: New Derivatives with Excellent Optical Performances, Convenient Synthesis, and Low Toxicity

“…Much different from the cells easily seen in Figure 4D in the presence of EB, those with EB‐BPh could hardly be observed (Figure 4B), clearly proving the low efficiency of EB‐BPh uptaken by cells. This result is also confirmed by flow cytometric analysis (Figure S14, Supporting Information) . These cell imaging results and cell uptake analysis match the Zeta potential values.…”

Rational Design of Nanocarriers for Intracellular Protein Delivery

“…[186] The conventional fabrication methods of enzyme-MOF composites were used organic solvent, which would easily denature enzymes. [190][191][192] Zhang et al used facile synthesis protocols to prepare protein embedded MOFs vaccines. Shieh et al developed a de novo approach under aqueous conditions to embed catalase into zeolitic imidazolate framework 90 (ZIF-90) supports of pore sizes smaller than the size of the enzyme.…”

“…It is urgent to pursue a facile and mild reaction conditions for the synthesis of composites to preserve enzymes' activities. [190] Lian et al www.advmat.de www.advancedsciencenews.com the nano-MOFs were localized inside lysosomes, they still keep their chemical stability and enzymatic activity against the protease degradation and low pH environment. The composites not only enhanced the stability and recyclability of the enzyme, but also retained the peroxidase activity of catalase.…”

DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy

“…[15,16] Despite the increasing interests in DNAzyme-mediated gene silencing,c hallenges still exist in its poor cellular delivery and ineffective intracellular DNAzyme cleavage originating from insufficient cofactor supply. MOFs are also utilized as robust solid scaffolds for anchoring nucleic acids through electrostatic adsorption, [23][24][25] covalent conjugation, [26][27][28] or van der Waals interactions, [29] yet they suffer from either environmental vulnerability or tedious assembly.MOFs have been introduced as robust vessels for siRNAo rD NAzymes without stimuli-responsiveness. MOFs are also utilized as robust solid scaffolds for anchoring nucleic acids through electrostatic adsorption, [23][24][25] covalent conjugation, [26][27][28] or van der Waals interactions, [29] yet they suffer from either environmental vulnerability or tedious assembly.MOFs have been introduced as robust vessels for siRNAo rD NAzymes without stimuli-responsiveness.…”