基于pH响应及抗原和CpG核酸共载的纳米疫苗运载体系的构建

doi:10.3969/j.issn.1674-490X.2016.04.001

医学研究与教育 ›› 2016, Vol. 33 ›› Issue (4): 1-6.DOI: 10.3969/j.issn.1674-490X.2016.04.001

• 基础医学 • 下一篇

基于pH响应及抗原和CpG核酸共载的纳米疫苗运载体系的构建

李振华¹,尹璇², 王烨莲²,赵宝成²,段飞¹

1. 河北大学化学与环境科学学院, 河北保定 071002;
2.保定市第一中心医院, 河北保定 071000

收稿日期:2016-07-01 出版日期:2016-08-25 发布日期:2016-08-25
作者简介:李振华(1986—),男,河北遵化人,副教授,博士,主要从事纳米医学及化学生物学相关领域的研究。 E-mail: zhenhuali1013@163.com
基金资助:
保定市科技支撑计划项目(15ZF055)

Establishment of nanovaccines for dual-delivery of antigens and CpG nucleic acid

LI Zhenhua¹, YIN Xuan², WANG Yelian², ZHAO Baocheng², DUAN Fei¹

1. College of Chemistry& Environmental Science, Hebei University, Baoding 071002, China; 2. The First Center Hospital of Baoding, Baoding 071000, China

Received:2016-07-01 Online:2016-08-25 Published:2016-08-25

摘要/Abstract

摘要： 目的建立一种有效的抗原和免疫激动剂共载体系解决抗原被抗原呈递细胞内吞效率低、免疫活性低、易降解等问题。方法选择介孔硅为核,负载模式抗原鸡卵清白蛋白(OVA)后,用Eu³⁺及鸟嘌呤单核苷酸(GMP)形成的金属有机框架结构(MOF)包覆在介孔硅表面,并在其表面吸附免疫刺激剂CpG核酸,构建pH敏感的抗原和免疫刺激剂的共载体系。结果介孔硅对抗原负载率为20%,且在酸性条件下孵育24 h后其蛋白释放量达到55%;透射电镜结果表明共轭聚合物均匀包覆在材料表面;通过紫外吸收光谱实验计算得出载体对CpG核酸的吸附能力为每毫克的载体吸附核酸的物质的量为1.8×10^-6 mol;MTT结果表明,载体具有较低的毒性。结论介孔硅对抗原具有较高的负载率,并且共轭聚合物成功包覆于介孔硅表面,不仅对抗原进行保护,而且能将免疫激动剂核酸吸附在材料表面,更重要的是载体具有pH响应释放的能力。

关键词: 蛋白疫苗, 纳米载体, pH响应, CpG核酸

Abstract: Objective To establish effective nonvaccines to solve the problems of low internalized efficiency by antigen presenting cell, low immune activity and easy to be degraded in vivo. Methods Mesoporous silica nanoparticles(MSN)were chosen as the core for antigens(ovalbumin, OVA)loading. Then metal organic frameworks(MOFs)formed by Eu³⁺ and guanine nucleotide(GMP)were coated on the surface of MSN. After adsorption of CpG oligonucleotides, we constructed pH-responsive nanovaccines for dual-delivery of antigens and CpG. Results The loading capability of mesoporous silica was 20%, and the release rate of antigens could reach to 55% after incubation for 24 h under acidic conditions. The results of transmission electron microscope indicated that MOFs were coated on the surface of MSN, the loading capability of nanocarriers for CpG was 1.8×10^-6 mol of nucleic acid per mg of nanoparticles,nanocarriers showed low cytotoxicity analyzed by MTT. Conclusion A novel nanovaccine is constructed and the introduction of MOFs can protect the antigens from degradation and enhance the adsorption rate of nanocarriers. Furthermore, antigens can be released under acidic conditions, which can enhance the immune response in the future.

Key words: protein-based vaccines, nanocarriers, pH-responsive, CpG nucleic acid

中图分类号:

R392.11

李振华,尹璇, 王烨莲,赵宝成,段飞. 基于pH响应及抗原和CpG核酸共载的纳米疫苗运载体系的构建[J]. 医学研究与教育, 2016, 33(4): 1-6.

LI Zhenhua, YIN Xuan, WANG Yelian, ZHAO Baocheng, DUAN Fei. Establishment of nanovaccines for dual-delivery of antigens and CpG nucleic acid[J]. Medical Reserch and Education, 2016, 33(4): 1-6.

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基于pH响应及抗原和CpG核酸共载的纳米疫苗运载体系的构建

Establishment of nanovaccines for dual-delivery of antigens and CpG nucleic acid

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