高等学校化学学报 ›› 2020, Vol. 41 ›› Issue (7): 1461-1469.doi: 10.7503/cjcu20200242

• 庆祝《高等学校化学学报》复刊40周年专栏 • 上一篇    下一篇

基于DNA纳米花的细胞自噬基因沉默用于增敏抗肿瘤化疗

张开翔1,2,刘军杰1,宋巧丽1,王丹钰1,史进进1,*(),张海悦3,*(),李景虹2,*()   

  1. 1.郑州大学药学院, 河南省肿瘤重大疾病靶向治疗与诊断重点实验室, 郑州450001
    2.清华大学化学系, 北京100084
    3.长春工业大学化学与生命科学学院, 长春130012
  • 收稿日期:2020-04-29 出版日期:2020-07-10 发布日期:2020-06-02
  • 通讯作者: 史进进,张海悦,李景虹 E-mail:shijinyxy@zzu.edu.cn;zhhaiyue@163.com;jhli@mail.tsinghua.edu.cn
  • 基金资助:
    国家自然科学基金(21904119);国家自然科学基金(21621003);河南省科技攻关项目(192102310147)

Multifunctional DNA Nanoflowers for Autophagy Inhibition and Enhanced Antitumor Chemotherapy

ZHANG Kaixiang1,2,LIU Junjie1,SONG Qiaoli1,WANG Danyu1,SHI Jinjin1,*(),ZHANG Haiyue3,*(),LI Jinghong2,*()   

  1. 1. Key laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
    2. Department of Chemistry, Tsinghua University, Beijing 100084, China
    3. College of Chemical and Life Science, Changchun University of Technology, Changchun 130012, China
  • Received:2020-04-29 Online:2020-07-10 Published:2020-06-02
  • Contact: Jinjin SHI,Haiyue ZHANG,Jinghong LI E-mail:shijinyxy@zzu.edu.cn;zhhaiyue@163.com;jhli@mail.tsinghua.edu.cn
  • Supported by:
    † National Natural Science Foundation of China(21904119);National Natural Science Foundation of China(21621003);Key Scientific Research Projects of Science and Technology Department of Henan Province, China(192102310147)

摘要:

自噬是真核细胞降解蛋白质的重要途径之一, 在细胞的更新代谢中起重要作用. 肿瘤细胞借助高水平的细胞自噬能够阻断细胞凋亡途径, 降低化疗药物的抗肿瘤效果. 本文通过设计编码有核酸适配体序列(Aptamer)和DNA酶序列(DNAzyme)的多功能DNA纳米花, 利用DNA序列可负载化疗药物阿霉素(Dox)的特性, 实现了对肿瘤细胞特异靶向的药物递送, 并高效沉默肿瘤细胞的自噬相关基因ATG5, 达到增敏抗肿瘤化疗的效果. 通过RT-PCR实验验证合成的DNA纳米花可以有效剪切肿瘤细胞中自噬相关基因ATG5的mRNA; 并通过DNA纳米花的细胞毒性和细胞凋亡实验研究了其对肿瘤细胞系MCF-7的靶向治疗作用, 结果显示该多功能DNA纳米花在增敏抗肿瘤化疗方面具有明显优势.

关键词: DNA纳米花, 药物递送, 自噬, DNA酶, 抗肿瘤化疗

Abstract:

Autophagy is an important process in eukaryotic cells, in which subcellular membranes undergo dynamic morphological changes, leading to the degradation of cellular proteins and cytoplasmic organelles. High levels of cellular autophagy could protect tumor cells from apoptosis and reduce the antitumor effect of chemotherapy drugs. In this work, we designed a multifunctional DNA nanoflower, which encode DNA aptamer and DNAzyme for targeted drug delivery and gene silencing to inhibit autophagy in tumor cells. Using RT-PCR, we verified that the designed DNA nanoflower can effectively cleave the mRNA of autophagy-related gene(ATG5) in tumor cells. The cytotoxicity and cell apoptosis assay also showed that the synthesized multifunctional DNA nanoflower could enhance antitumor chemotherapy.

Key words: DNA nanoflowers, Drug delivery, Autophagy, DNAzyme, Antitumor chemotherapy

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