Structural characterization of a novel fucoidan from Sargassum horneri for anticancer drug delivery

IF 2.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xue Liu , Wen Zhao , Xinyue Gai , Tuoyu Ju , Miansong Zhang , Tingting Cui , Hongfang Du , Airong Jia
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Abstract

A fucoidan SHF from Sargassum horneri was obtained. Nanoparticles were prepared using SHF (F) and chitosan (Cs) at F/Cs mass ratios of 1.0/3.0, 1.0/1.5, 1.0/1.0, 1.5/1.0 and 3.0/1.0. The nanoparticles showed a high binding affinity for P-selectin, especially at the ratio of 1.5/1.0. The pH-responsive drug release of doxorubicin (DOX)-loaded nanoparticles was evaluated to select the nanoparticle with low DOX release in blood (pH 7.4) but high release upon entering the endosome/lysosome (pH 4.5–5.5) of cancer cells. Results indicated that the DOX release rate significantly increased at 1.5/1.0 when the medium pH decreased from 7.4 to 5.5. Moreover, DOX-loaded nanoparticles showed improved inhibitory effects against a metastatic breast cancer cell line (MDA-MB-231) compared to free DOX at equivalent concentrations. Therefore, nanoparticles based on SHF achieved efficient delivery of DOX. SHF is an excellent material for the tumor-targeting drug delivery systems. To further understand the structural characteristics of tumor-targeting fucoidan, the fine structure of SHF was analyzed. The main chain of SHF might be cross-linked by →4)-α-l-Fucp(2,3SO4)-(1→ and →3,2)-β-d-Galp-(1→, with the →4,6)-β-d-Manp-(1 → 3,2)-β-d-Galp-(1 → 4,6)-β-d-Manp-(1→ fragment interspersed between them. Notably, dual-sulfated fucose residues accounted for a large proportion.

Abstract Image

一种用于抗癌药物传递的新型马尾藻褐藻聚糖的结构表征
从马尾藻中获得了褐藻糖胶 SHF。利用 SHF(F)和壳聚糖(Cs)制备了纳米颗粒,F/Cs 的质量比分别为 1.0/3.0、1.0/1.5、1.0/1.0、1.5/1.0 和 3.0/1.0。纳米颗粒与 P-选择素的结合亲和力很高,尤其是在 1.5/1.0 的比例下。评估了负载多柔比星(DOX)的纳米颗粒的 pH 值响应药物释放情况,以筛选出在血液中(pH 值为 7.4)DOX 释放率低,但进入癌细胞内膜/溶酶体(pH 值为 4.5-5.5)后释放率高的纳米颗粒。结果表明,当培养基 pH 值从 7.4 降至 5.5 时,DOX 释放率在 1.5/1.0 时显著增加。此外,与等浓度的游离 DOX 相比,DOX 负载纳米颗粒对转移性乳腺癌细胞系(MDA-MB-231)的抑制效果更好。因此,基于 SHF 的纳米颗粒实现了 DOX 的高效递送。SHF是肿瘤靶向给药系统的极佳材料。为了进一步了解肿瘤靶向褐藻糖胶的结构特征,我们对SHF的精细结构进行了分析。SHF的主链可能由→4)-α-l-Fucp(2,3SO4)-(1→和→3,2)-β-d-Galp-(1→交联而成,其间夹杂着→4,6)-β-d-Manp-(1→3,2)-β-d-Galp-(1→4,6)-β-d-Manp-(1→片段。值得注意的是,双硫酸化岩藻糖残基占了很大比例。
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来源期刊
Carbohydrate Research
Carbohydrate Research 化学-生化与分子生物学
CiteScore
5.00
自引率
3.20%
发文量
183
审稿时长
3.6 weeks
期刊介绍: Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".
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