College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu 210095, P.R. China.
Key Laboratory of Synthetic Rubber, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P.R. China.
ACS Nano. 2020 Mar 24;14(3):2760-2776. doi: 10.1021/acsnano.9b09125. Epub 2020 Jan 24.
It is a desirable and powerful strategy to precisely fabricate functional soft matter through self-assembly of molecular building blocks across a range of length scales. Proteins, nucleic acids, and polyphenols are the self-assemblers ubiquitous in nature. Assembly of proteins into flexible biocolloids, amyloid fibrils with high aspect ratio, has emerged as an unchallenged templating strategy for high-end technological materials and bio-nanotechnologies. We demonstrate the ability of these fibrils to support the deposition and self-assembly of polyphenols into hybrid nanofilaments and functional macroscopic hydrogels made thereof. The length scale of the substance that amyloid fibrils can attach with acting as the building templates was extended from nanometer down to sub-nanometer. Significantly increased loading capacities of polyphenols (up to 4.0 wt %) compared to that of other delivery systems and improved stability were realized. After oral administration, the hydrogels could transport from the stomach to the small intestine and finally to the gut (cecum, colon, rectum), with a long retention time in the colon. Oral administration of the hydrogels significantly ameliorated colitis in a mouse model, promoted intestinal barrier function, suppressed the pro-inflammatory mRNA expression, and very significantly ( < 0.01) regulated gut microbial dysbiosis. Specifically, it reduced the abundance of normally enriched operational taxonomic units related to colitis, especially targeting facultative anaerobes of the phylum Proteobacteria, such as and . The short-chain fatty acid metabolites were enriched. Combined with their nontoxic nature observed in this long-term study in mice, the obtained amyloid-polyphenol gels have high application potentials for gastrointestinal diseases by "drugging the microbiome".
通过分子构建块在一系列长度尺度上的自组装来精确构建功能软物质是一种理想且强大的策略。蛋白质、核酸和多酚是自然界中无处不在的自组装体。蛋白质组装成具有高纵横比的柔性生物胶体、淀粉样原纤维，已成为高端技术材料和生物纳米技术的无可挑战的模板策略。我们证明了这些纤维能够支持多酚沉积和自组装成混合纳米纤维，并由此制成功能性宏观水凝胶。淀粉样原纤维可以附着并用作构建模板的物质的长度尺度从纳米延伸到亚纳米。与其他输送系统相比，多酚的负载能力显著提高（高达 4.0wt%），稳定性也得到提高。口服后，水凝胶可以从胃运送到小肠，最终运送到肠道（盲肠、结肠、直肠），在结肠中停留时间长。水凝胶的口服给药可显著改善小鼠模型中的结肠炎，促进肠道屏障功能，抑制促炎 mRNA 表达，并非常显著（<0.01）调节肠道微生物失调。具体而言，它减少了与结肠炎相关的通常丰富的操作分类单元的丰度，特别是针对厚壁菌门 Proteobacteria 中的兼性厌氧菌，如 和 。短链脂肪酸代谢物被富集。结合在小鼠中进行的这项长期研究中观察到的它们的无毒性质，获得的淀粉样蛋白-多酚凝胶通过“药物微生物组”对胃肠道疾病具有很高的应用潜力。
