Department of Oncology of the First Affiliated Hospital, Department of Chemistry, Jinan University, Guangzhou 510632, China.
School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
J Am Chem Soc. 2023 Jun 7;145(22):12193-12205. doi: 10.1021/jacs.3c02179. Epub 2023 May 19.
Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.
硒蛋白在免疫细胞和炎症调节中发挥着关键作用。然而，由于硒蛋白在胃的酸性环境中容易变性或降解，因此高效的口服递送硒蛋白是一个巨大的挑战。在此，我们创新性地提出了一种基于口服水凝胶微球的生化策略，该策略可以原位合成硒蛋白，从而避免了口服蛋白递送的必要性和苛刻条件，同时有效地生成用于治疗应用的硒蛋白。水凝胶微球是通过用海藻酸钠（SA）水凝胶的保护层包覆透明质酸修饰的硒纳米颗粒来合成的。我们在炎症性肠病（IBD）的小鼠中测试了这种策略，IBD 是与肠道免疫和微生物群关系最密切的代表性疾病之一。我们的结果表明，水凝胶微球介导的硒蛋白原位合成可以显著减少促炎细胞因子的分泌，并介导免疫细胞（例如，减少中性粒细胞和单核细胞，增加免疫调节性 T 细胞），从而有效缓解结肠炎相关症状。该策略还可以调节肠道微生物群组成（增加益生菌丰度并抑制有害菌群）以维持肠道内稳态。鉴于肠道免疫和微生物群与癌症、感染、炎症等广泛相关，这种原位硒蛋白合成策略也可能被广泛应用于治疗各种疾病。
