小粒径Fe3O4-DMSA-PEI磁性纳米颗粒的制备及其基因负载能力研究

doi:10.15541/jim20230464

无机材料学报 ›› 2024, Vol. 39 ›› Issue (5): 517-524.DOI: 10.15541/jim20230464 CSTR: 32189.14.10.15541/jim20230464

所属专题：【生物材料】肿瘤治疗(202409)

小粒径Fe₃O₄-DMSA-PEI磁性纳米颗粒的制备及其基因负载能力研究

蔡和庆¹(), 韩璐¹(), 杨松松¹, 薛新玉¹, 张扣¹, 孙志成¹, 刘儒平¹, 胡堃¹, 危岩²()

1.北京印刷学院印刷与包装工程学院, 北京 102600
2.清华大学生命有机磷化学及化学生物学教育部重点实验室, 北京 100084

收稿日期:2023-10-09 修回日期:2023-12-07 出版日期:2024-05-20 网络出版日期:2023-12-25
通讯作者: 韩璐, 副教授. E-mail: hanlu@iccas.ac.cn;
危岩, 教授. E-mail: weiyen@tsinghua.edu.cn
作者简介:蔡和庆(1997-), 男, 硕士研究生. E-mail: 724040386@qq.com
基金资助:
国家自然科学基金(61971049);国家自然科学基金(62211530446);国家自然科学基金(22278037);北京印刷学院科研创新团队项目(Ea202205);北京市高等教育学会2023年立项重点课题(ZD202312)

Fe₃O₄-DMSA-PEI Magnetic Nanoparticles with Small Particle Size: Preparation and Gene Loading

CAI Heqing¹(), HAN Lu¹(), YANG Songsong¹, XUE Xinyu¹, ZHANG Kou¹, SUN Zhicheng¹, LIU Ruping¹, HU Kun¹, WEI Yan²()

1. School of Printing and Packaging Engineering, Beijing Institute of Graphic Communication, Beijing 102600, China
2. Key Laboratory of Organophosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing 100084, China

Received:2023-10-09 Revised:2023-12-07 Published:2024-05-20 Online:2023-12-25
Contact: HAN Lu, associate professor. E-mail: hanlu@iccas.ac.cn;
WEI Yan, professor. E-mail: weiyen@tsinghua.edu.cn
About author:CAI Heqing (1997-), male, Master candidate. E-mail: 724040386@qq.com
Supported by:
National Natural Science Foundation of China(61971049);National Natural Science Foundation of China(62211530446);National Natural Science Foundation of China(22278037);Scientific Research Innovation Project from Beijing Institute of Graphic Communication(Ea202205);The 2023 Key Project from Beijing Association of Higher Education(ZD202312)

摘要/Abstract

摘要：

四氧化三铁(Fe₃O₄)磁性纳米颗粒因其制备简单, 在外加磁场作用下具有靶向性，并且表面易接枝等特性, 可作为被动靶向载体应用于基因治疗领域。本研究采用溶剂热法制备纳米颗粒, 并调控堆积生长时间, 制得粒径在4~9 nm范围内可控的油相Fe₃O₄纳米颗粒; 使用内消旋-2,3-二巯基丁二酸(DMSA)二次取代其表面的油酸分子, 使其具备良好的水相分散性; 通过酰胺化反应在其表面接枝支链型聚乙烯亚胺(PEI), 最终得到Fe₃O₄-DMSA-PEI磁性纳米颗粒。研究发现, Fe₃O₄-DMSA-PEI磁性纳米颗粒的表面Zeta电位高达(52.50±1.94) mV, 具有一定的超顺磁性(14.48 emu/g, 1 emu/g=1 A∙m²/kg)。磁性纳米颗粒与质粒DNA的质量比为15 : 1时可完全阻滞DNA在凝胶上的电泳, 装载量高达6.67%。本研究制备的Fe₃O₄-DMSA-PEI磁性纳米颗粒具有一定的基因负载能力, 有望作为基因载体应用于基因转染领域。

关键词: 四氧化三铁, 磁性纳米颗粒, 基因载体, 表面改性

Abstract:

Ferroferric oxide (Fe₃O₄) magnetic nanoparticles are widely used as passive targeting carriers in gene therapy, due to their simple preparation, targeting under external magnetic field and easy surface grafting. This study synthesized oil phase Fe₃O₄ nanoparticles with controllable particle sizes in the range from 4 to 9 nm by regulating the accumulation growth time in the solvothermal method. Then, meso-2, 3-dimercaptosuccinic (DMSA) was employed to double exchange oleic acid molecules on its surface to provide good water dispersibility. Finally, Fe₃O₄-DMSA-PEI magnetic nanoparticles were obtained by grafting branched polyethylenimine (PEI) onto Fe₃O₄-DMSA surface through amidization reaction. The results demonstrate that the Fe₃O₄-DMSA-PEI magnetic nanoparticles have a surface Zeta potential of (52.50 ± 1.94) mV, remaining a certain degree of superparamagnetism (14.48 emu/g, 1 emu/g=1 A∙m²/kg). When the mass ratio of Fe₃O₄-DMSA-PEI magnetic nanoparticles to plasmid DNA is 15 : 1, it can completely block DNA and its loading capacity is as high as 6.67%. The Fe₃O₄-DMSA-PEI magnetic nanoparticles prepared in this study have a certain gene delivery ability and are expected to be used as gene carriers in the field of gene transfection.

Key words: ferroferric oxide, magnetic nanoparticle, gene carrier, surface modification

中图分类号:

TB383

蔡和庆, 韩璐, 杨松松, 薛新玉, 张扣, 孙志成, 刘儒平, 胡堃, 危岩. 小粒径Fe₃O₄-DMSA-PEI磁性纳米颗粒的制备及其基因负载能力研究[J]. 无机材料学报, 2024, 39(5): 517-524.

CAI Heqing, HAN Lu, YANG Songsong, XUE Xinyu, ZHANG Kou, SUN Zhicheng, LIU Ruping, HU Kun, WEI Yan. Fe₃O₄-DMSA-PEI Magnetic Nanoparticles with Small Particle Size: Preparation and Gene Loading[J]. Journal of Inorganic Materials, 2024, 39(5): 517-524.

图/表 10

图1 Fe3O4纳米颗粒表面嫁接PEI的路线图

Fig. 1 Route map of PEI grafting on the surface of Fe3O4 nanoparticles

图2 Fe3O4-OA的TEM照片

Fig. 2 TEM images of Fe3O4-OA (a) MNP-1; (b) MNP-2; (c) MNP-3

图3 样品的粒径分布(a, c)和分散性(b, d)

Fig. 3 Particle size distributions (a, c) and polydispersity indexs (b, d) of samples (a, b) Fe3O4-OA (MNP-1, MNP-2 and MNP-3); (c, d) Fe3O4-OA, Fe3O4-DMSA and Fe3O4-DMSA-PEI Colorful figures are available on website

图4 Fe3O4-OA, Fe3O4-DMSA和Fe3O4-DMSA-PEI的FT-IR图谱

Fig. 4 FT-IR spectra of Fe3O4-OA, Fe3O4-DMSA and Fe3O4-DMSA-PEI

图5 Fe3O4-OA和Fe3O4-DMSA的拉曼图谱

Fig. 5 Raman spectra of Fe3O4-OA and Fe3O4-DMSA

图6 Fe3O4-DMSA-PEI的XRD图谱

Fig. 6 XRD pattern of Fe3O4-DMSA-PEI

图7 Fe3O4-OA, Fe3O4-DMSA和Fe3O4-DMSA-PEI的Zeta电位图

Fig. 7 Zeta potential histogram of Fe3O4-OA, Fe3O4-DMSA and Fe3O4-DMSA-PEI

图8 (a)Fe3O4-OA, (b)Fe3O4-DMSA和(c, d)Fe3O4-DMSA-PEI的变温磁感应曲线

Fig. 8 Variable temperature magnetic induction curves of (a) Fe3O4-OA, (b) Fe3O4-DMSA and (c, d) Fe3O4-DMSA-PEI

图9 Fe3O4-OA, Fe3O4-DMSA和Fe3O4-DMSA-PEI的磁滞回线

Fig. 9 Hysteresis loops of Fe3O4-OA, Fe3O4-DMSA and Fe3O4-DMSA-PEI 1 emu/g=1 A∙m2/kg; 1 Oe=79.6 A/m

图10 Fe3O4-DMSA-PEI(1800)阻滞质粒DNA的凝胶电泳照片

Fig. 10 Gel electrophoresis image of Fe3O4-DMSA-PEI(1800) blocking plasmid DNA

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小粒径Fe₃O₄-DMSA-PEI磁性纳米颗粒的制备及其基因负载能力研究

Fe₃O₄-DMSA-PEI Magnetic Nanoparticles with Small Particle Size: Preparation and Gene Loading

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