Dai Wanting, Song Xiaoxiao, Wang Rui, He Weiwei, Yin Junyi, Nie Shaoping
State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang 330047, China.
State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang 330047, China.
J Control Release. 2025 Mar 10;379:524-536. doi: 10.1016/j.jconrel.2025.01.023. Epub 2025 Jan 21.
Selenium deficiency associated with a high risk of many diseases remains a global challenge. Owing to the narrow margin between "nutrition-toxicity" doses of selenium, it is imperative to achieve accurate selenium supplement. Nano‑selenium (SeNPs) is a novel form of selenium supplement with low toxicity, but it could be trapped and removed by intestinal mucus, thus limiting its oral delivery. The mucus penetration of SeNPs is highly associated with interactions between SeNPs and mucin (the structural component of mucus). In this study, we selected four polysaccharides with different functional groups and molecular weights, i.e. chitosan oligosaccharide (COS), chitosan (CS), chitosan quaternary ammonium salt (HACC), and carboxymethyl cellulose (CMC) as templates to modify SeNPs. Then we systematically explored the non-covalent interactions between polysaccharides stabilized nano-Se (PS-SeNPs) and mucin, determined and examined mucus penetration behavior and mechanism of different PS-SeNPs by coarse-grained molecular dynamics simulations, both in vitro and in vivo. It could be observed that penetration of PS-SeNPs depends on their distinct surface properties and mucus pH conditions. COS-SeNPs with short oligosaccharide chains accumulated and bridged with mucin, hindering its mucus penetration at pH 7.4. While HACC-SeNPs with NH and N exhibited high binding affinity with mucin, inducing its mucus penetration. The negatively charged CMC-SeNPs diffused freely in mucus due to their electrostatic-repelled interaction and hydrophobic interaction with mucin. This study establishes a theoretical foundation for precise application of SeNPs in oral administration and offers valuable insights into the precise utilization of polysaccharides as tailored carriers of nanoparticles in mucus-covered tissues.
与多种疾病高风险相关的硒缺乏仍然是一个全球性挑战。由于硒的“营养 - 毒性”剂量区间狭窄，实现精准补硒势在必行。纳米硒（SeNPs）是一种低毒的新型硒补充形式，但它可能会被肠道黏液捕获并清除，从而限制其口服给药。SeNPs的黏液穿透性与SeNPs和黏蛋白（黏液的结构成分）之间的相互作用高度相关。在本研究中，我们选择了四种具有不同官能团和分子量的多糖，即壳寡糖（COS）、壳聚糖（CS）、壳聚糖季铵盐（HACC）和羧甲基纤维素（CMC）作为模板来修饰SeNPs。然后，我们系统地探索了多糖稳定化纳米硒（PS - SeNPs）与黏蛋白之间的非共价相互作用，通过粗粒度分子动力学模拟在体外和体内确定并研究了不同PS - SeNPs的黏液穿透行为及机制。可以观察到，PS - SeNPs的穿透取决于其独特的表面性质和黏液pH条件。具有短寡糖链的COS - SeNPs与黏蛋白聚集并桥连，在pH 7.4时阻碍其黏液穿透。而带有NH和N的HACC - SeNPs与黏蛋白表现出高结合亲和力，诱导其黏液穿透。带负电荷的CMC - SeNPs由于其与黏蛋白的静电排斥相互作用和疏水相互作用而在黏液中自由扩散。本研究为SeNPs在口服给药中的精准应用奠定了理论基础，并为多糖作为黏液覆盖组织中纳米颗粒的定制载体的精准利用提供了有价值的见解。
