硫酸化糖修饰Fe3O4@SiO2纳米粒子诱导肿瘤细胞凋亡研究

doi:10.7503/cjcu20180142

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (11): 2458.doi: 10.7503/cjcu20180142

硫酸化糖修饰Fe₃O₄@SiO₂纳米粒子诱导肿瘤细胞凋亡研究

袁嘉怿, 叶宝彤, 吴婧, 李颖, 陈敬华(), 陈荆晓()

糖化学与生物技术教育部重点实验室, 江南大学药学院, 无锡 214122

收稿日期:2018-02-21 出版日期:2018-11-10 发布日期:2018-09-22
作者简介:联系人简介: 陈敬华, 男, 博士, 教授, 主要从事糖药物和生物活性高分子研究. E-mail: chenjinghua@jiangnan.edu.cn; 陈荆晓, 男, 博士, 副教授, 主要从事生物医用高分子材料研究. E-mail: tomchenjx@jiangnan.edu.cn
基金资助:
国家自然科学基金(批准号: 21574059, 51303068)和中央高校基础科研业务费专项资金(批准号: JUSRP51709A)资助.

Study on Sulfated Glycosylated Fe₃O₄@SiO₂ Nanoparticles Inducing Tumor Cells Apoptosis^†

YUAN Jiayi, YE Baotong, WU Jing, LI Ying, CHEN Jinghua^*(), CHEN Jingxiao^*()

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China

Received:2018-02-21 Online:2018-11-10 Published:2018-09-22
Contact: CHEN Jinghua,CHEN Jingxiao E-mail:chenjinghua@jiangnan.edu.cn;tomchenjx@jiangnan.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21574059, 51303068) and the Fundamental Research Funds for the Central Universities, China(No.JUSRP51709A).

摘要/Abstract

摘要：

首先制备了具有磁性的Fe₃O₄@SiO₂纳米粒子, 然后通过“Click”化学反应在粒子表面修饰选择性保护的N-乙酰氨基葡萄糖, 再对糖硫酸化, 得到一系列具有核/壳结构、表面具有不同硫酸基图案的糖功能化的Fe₃O₄@SiO₂纳米粒子. 采用X射线衍射(XRD)、 X射线光电子能谱(XPS)和透射电子显微镜(TEM)等对Fe₃O₄@SiO₂纳米粒子修饰前后的成分和形貌进行了分析, 并从细胞水平初步研究了硫酸化糖修饰的Fe₃O₄@SiO₂纳米粒子诱导肿瘤细胞凋亡及对蛋白质信号的影响. 结果表明, 所制备的Fe₃O₄@SiO₂纳米粒子尺寸均一, 分散性良好, 经硫酸化糖修饰后, 平均粒径由110~130 nm增加至160~180 nm. 经硫酸化糖修饰后的纳米粒子能够有效进入肿瘤细胞, 调节Bcl-2/Bax通路的蛋白表达水平, 进而诱导细胞凋亡并呈现浓度依赖关系, 但不会影响正常细胞. 这一活性的差异与纳米粒子表面糖的硫酸基图案有关.

关键词: 硫酸化糖, 硫酸基图案, 细胞凋亡, Bcl-2/Bax通路, Fe₃O₄@SiO₂纳米粒子

Abstract:

Magnetic Fe₃O₄@SiO₂ nanoparticles(NPs) were first prepared through a solvothermal strategy, after that, selectively protected N-acetylglucosamine was modified on the surface of these NPs by “Click” chemistry, followed by sulfation to obtain a series of sulfated glycosylated Fe₃O₄@SiO₂ NPs with core/shell structure and various sulfation patterns. The components and morphology of these nanoparticles were characterized by X-ray diffraction(XRD), X-ray photoelectron spectroscopy(XPS) and transmission electron microscopy(TEM), respectively, before and after the modification. The effects of sulfated glycosyl groups on NPs-induced tumor cell apoptosis and protein signal regulation were studied. The results showed the prepared Fe₃O₄@SiO₂ NPs were uniform and well-dispersed. After the sulfated glycosylation, the average size of NPs increased from 110—130 nm to about 160—180 nm. These NPs could efficiently internalize into tumor cells, regulate the protein expression level of the Bcl-2/Bax pathway, and then induce cell apoptosis in a concentration-dependent manner. The activity was highly related to different sulfation patterns of glycosyl groups on the surface of NPs.

Key words: Sulfated glycosyl group, Sulfation pattern, cell apoptosis, Bcl-2/Bax pathway, Fe₃O₄@SiO₂ nanoparticles

中图分类号:

O614

TrendMD:

袁嘉怿, 叶宝彤, 吴婧, 李颖, 陈敬华, 陈荆晓. 硫酸化糖修饰Fe₃O₄@SiO₂纳米粒子诱导肿瘤细胞凋亡研究. 高等学校化学学报, 2018, 39(11): 2458.

YUAN Jiayi, YE Baotong, WU Jing, LI Ying, CHEN Jinghua, CHEN Jingxiao. Study on Sulfated Glycosylated Fe₃O₄@SiO₂ Nanoparticles Inducing Tumor Cells Apoptosis^†. Chem. J. Chinese Universities, 2018, 39(11): 2458.

图/表 11

Scheme 1 Synthetic route of a series of selectively protected N-acetylglucosamines

Fig.1 TEM images(A, B) and size distributions(C, D) of Fe3O4(A, C) and Fe3O4@SiO2(B, D) nanoparticles

Fig.2 XRD patterns of Fe3O4(a) and Fe3O4@SiO2(b)

Fig.3 XPS spectra of Fe3O4(A, B) and Fe3O4@SiO2(C, D) nanoparticles

Fig.4 TGA curves of Fe3O4@SiO2, alkynylated, and glycosylated nanoparticles(A), TEM image(B) and size distribution(C) of sulfated glycosylated nanoparticles and FTIR spectra of Fe3O4@SiO2, alkynylated, and sulfated glycosylated nanoparticles(D)

Table 1 Degree of substitution of sulfate groups on the surface of sulfated glycosylated nanoparticles

Compound	Glycosyl density/(nmol·cm^-2)	Sulfation pattern	Content of sulfate group(%)	Sulfation ratio of hydroxyl group^*(%)
1	1.35	3,4,6-S	51	63
2	0.45	6-S	28.5	69
3	0.50	3,6-S	42	64

Fig.5 XRD patterns(A) and XPS spectra(B) of sulfated glycosylated nanoparticles

Fig.6 Cell viability of Fe3O4@SiO2, sulfated N-acetylglucosamines, non-sulfated and sulfated glycosylated nanoparticles against COS7(A—C) and MGC-803(B—F) cells

Fig.7 Flow cytometric analysis(A, B) and count of MGC-803 cells(A', B') after incubating with sulfated glycosylated nanoparticles of different sulfation patterns(A, A') and 3,4,6-S nanoparticles of diffe-rent concentrations(B, B')

Fig.8 Western blot analysis of the effects of 3,4,6-sulfated glycosylated nanoparticles on Bcl-2/Bax pathway proteins of MGC-803 cellsGAPDH levels are shown as a protein loading control.

Scheme 2 Preparation of sulfated glycosylated nanoparticles(Ⅰ) and induced cancer cell apoptosis(Ⅱ)

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硫酸化糖修饰Fe₃O₄@SiO₂纳米粒子诱导肿瘤细胞凋亡研究

Study on Sulfated Glycosylated Fe₃O₄@SiO₂ Nanoparticles Inducing Tumor Cells Apoptosis^†

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