Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment
Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment
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果胶钙和透明质酸修饰乳铁蛋白纳米粒负载大黄酸双靶向治疗溃疡性结肠炎
DOI：
10.1016/j.carbpol.2021.117998
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发表时间：
2021-04-01
影响因子：
11.2
通讯作者：
Gao, Fei
中科院分区：
文献类型：
--
作者：
Luo, Ruifeng;Lin, Meisi;Gao, Fei
本研究将大黄酸（Rhein，RH）促进结肠黏膜损伤修复和控制炎症反应的双重生物效应与双靶向（肠上皮细胞和巨噬细胞）口服纳米给药策略相结合，用于溃疡性结肠炎（UC）的有效治疗。简言之，两种碳水化合物，果胶酸钙（CP）和透明质酸（HA）用于修饰乳铁蛋白（LF）纳米颗粒（NP）以包封RH（CP/ HA/RH-NP）。CP层使CP/HA/RH-NPs更稳定，并保护免受胃肠道环境的破坏作用，然后将HA/RH-NPs释放到结肠病变部位。细胞摄取评估证实，NP可以特异性地靶向并通过LF和HA配体增强摄取速率。体内实验显示CP/HA/RH-NPs通过抑制TLR 4/MyD 88/NF？B信号通路和加速结肠愈合。重要的是，在CP的帮助下，这项研究首次尝试将LF作为UC治疗中的靶向纳米材料，并提供了一种有前途的抗UC食品纳米药物。
Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/ HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF?B signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in antiUC.