Wen Guo,Zhiqi Wang,Rubing Xue,Xinyue Zhang,Qinfu Zhao,Yikun Gao,Siling Wang,Yuling Mao
Weak response is the bottleneck for subunit prophylactic vaccines to trigger efficient immunization. The emergence of highly effective adjuvants will revolutionize. Considering that genomic epigenetic reprogramming plays an important role in the immune response, we herein present an minimalist epigenetic nano-adjuvant gMSN constructed of β-glucan-modified functional mesoporous silica (MSN), which we term as OVA/gMSN after loaded with the model antigen ovalbumin (OVA). Oral administration of OVA/gMSN ensures that enough antigen reach dendritic cells (DCs) in intestinal mucosal lymphoid follicles via intestinal M cells while relying on gMSN to exhibit good adjuvant properties to trigger an effective systemic co-mucosal immune response. gMSN upregulates genes associated with aerobic glycolysis, promoting metabolic reprogramming in DCs and enhancing the expression of genes related to DC activation, cross-presentation, maturation, and migration. Simultaneously, it increases the accumulation of key epigenetic markers H3K27ac, H3K4me1, and H3K4me3. ATAC-seq results reveal enhanced chromatin accessibility of key immune genes, such as Il2rα1, Il18r1, and Cd83, in gMSN-treated DCs. This integrative molecular mechanism demonstrates that gMSN induces epigenomic remodeling in DCs after oral administration, showcasing the potential of combining epigenetic adjuvants and nanotechnology in oral vaccine design, and providing new directions and a theoretical basis for vaccine adjuvant development.
In this work, a novel core–shell structured gold@graphitized mesoporous silica nanocomposite (Au@GMSN) was synthesized by in situ graphitization of template within the mesochannels of mesoporous silica shell on gold core and demonstrated to be promising nanomaterials for surface-assisted laser desorption/ionization time-of-flight mass spectroscopy (SALDI-TOF MS). The integration of the graphitized mesoporous silica with the gold nanoparticles endowed Au@GMSN with large surface areas of graphitic structure, good dispersibility, and strong ultraviolet (UV) absorption. Au@GMSN exerted the synergistic effect on the efficient detection of small-molecular-weight analytes including amino acids, neutral saccharides, peptides, and traditional Chinese medicine. The Au@GMSN-assisted laser desorption/ionization exhibited the following superiorities: high ionization efficiency, low fragmentation interference, favorable salt tolerance, and good reproducibility. Moreover, because of the large hydrophobic inner surface area of the graphitized mesoporous silica shell, the Au@GMSN demonstrated its promising capacity in the pre-enrichment of aromatic analytes prior to SALDI-TOF MS, which favored rapid and sensitive detection.
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