应用化学 ›› 2021, Vol. 38 ›› Issue (6): 693-703.DOI: 10.19894/j.issn.1000-0518.200302

• 研究论文 • 上一篇    下一篇

石墨烯纳米载药体系的制备及对肿瘤细胞的杀伤作用

张雅静1, 王晓辉3, 徐亚娟4, 刘文书2*, 赵丽辉1*   

  1. 1长春理工大学生命科学技术学院,长春 130022
    2吉林大学第一临床医院口腔科,长春 130012
    3中国科学院长春应用化学研究所,化学生物学实验室,长春 130022
    4吉林省肿瘤医院口腔颌面外科,长春 130012
  • 收稿日期:2020-10-06 修回日期:2020-12-16 出版日期:2021-06-01 发布日期:2021-08-01
  • 通讯作者: *E-mail:1252042806@qq.com; 535923996@qq.com
  • 基金资助:
    吉林省科技厅(No.JJKH20170604KJ)项目资助

Preparation of Graphene Nano-Drug Carrier System and Its Killing Effect on Tumor Cells

ZHANG Ya-Jing1, WANG Xiao-Hui3, XU Ya-Juan4, LIU Wen-Shu2*, ZHAO Li-Hui1*   

  1. 1College of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, China
    2Department of Stomatology, the First Clinical Hospital of Jilin University, Changchun 130012, China
    3Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
    4Oral and Maxillofacial Surgery, Jilin Cancer Hospital, Changchun 130012, China
  • Received:2020-10-06 Revised:2020-12-16 Online:2021-06-01 Published:2021-08-01
  • Supported by:
    Science and Technology Department of Jilin Province (No.JJKH20170604KJ)

摘要: 通过聚乙二醇(PEG)及分支型聚乙烯亚胺(bPEI)对纳米氧化石墨烯(NGO)修饰作为大分子载药基底的载药平台,增加了NGO的水溶性及其对蛋白的吸附作用,随后分别负载抗癌药物顺铂(CDDP)和低温乙醇法分离提纯的肿瘤患者血清形成能够特异性富集于鼻咽癌细胞的大分子石墨烯纳米载药体系。通过紫外-可见光谱和傅里叶变换红外光谱表征结果证实NGO-PEG-bPEI-CDDP载药体系制备成功,NGO-PEG-bPEI对CDDP的载药率为34.6%。 聚丙烯酰胺凝胶电泳(SDS-PAGE)表明对NGO-PEG-bPEI-CDDP-Antibody大分子纳米载药体系中特异性抗体蛋白的强烈吸附作用,该纳米复合物能够特异性地富集在肿瘤细胞部位,对人鼻咽癌细胞(CNE-1)细胞系的识别极其敏感。细胞毒性实验(MTT)检测实验结果表明:在相同剂量(质量浓度)、相同作用时间的情况下,NGO-PEG-bPEI-CDDP-Antibody大分子纳米石墨烯载药体系兼具对人口腔鳞癌细胞(KB)、CNE-1杀伤作用和避免正常细胞的额外损伤。 NGO-PEG-bPEI-CDDP-Antibody纳米载药体系不仅能够通过特异性识别将药物富集于病灶区降低正常细胞损害,还能够有效杀伤癌细胞,降低化疗药物使用剂量,是一种很有前景的大分子纳米载药体系。

关键词: 纳米氧化石墨烯, 大分子载药体系, 肿瘤特异性抗体, 肿瘤富集作用

Abstract: In this study, a nano-graphene oxide (NGO) was modified by polyethylene glycol (PEG) and branched polyethyleneimine (bPEI) as a drug loading platform of macromolecular drugs, which increases the water solubility of NGO and the adsorption of proteins. Then, tumor patient serum was prepared by loading anti-cancer drug cis-diamminedichloroplatinum (CDDP) and low-temperature ethanol, respectively, to form the graphene nanoparticle drug delivery system. The ultraviolet-visible and Fourier transform infraredspectroscopy characterization results demonstrate that the NGO-PEG-bPEI-CDDP drug loading system is successfully prepared, and the drug loading rate of NGO-PEG-bPEI to CDDP is 34.6%. Polyacrylamide gel electrophoresis (SDS-PAGE) demonstrates strong adsorption of specific antibody proteins in the NGO-PEG-bPEI-CDDP-Antibody macromolecular nano-loading system, and the nanocomposite can be specifically enriched in tumors. Cell sites are extremely sensitive to the recognition of CNE-1 cell lines. Cytotoxicity test (MTT) results demonstrate that the drug delivery system of NGO-PEG-bPEI-CDDP-Antibody macromolecular nano graphene can kill KB and CNE-1 cells and avoid additional damage to normal cells at the same concentration and time. The NGO-PEG-bPEI-CDDP-Antibody nano drug-loading system can not only enrich the drug in the lesion area through specific recognition, reduce normal cell damage, but also effectively kill cancer cells and reduce the dose of chemotherapy drugs, which is a very promising macromolecular nano-drug loading system.

Key words: Nano-graphene oxide, Macromolecular drug loading system, Tumor-specific antibody, Tumor enrichment

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