Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy

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Abstract

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca 2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.

Original languageEnglish
Article number3684
Number of pages20
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 1 May 2024
MoE publication typeA1 Journal article-refereed

Keywords

  • Stomach Neoplasms/metabolism
  • Humans
  • Aptamers, Nucleotide/chemistry
  • Cell Line, Tumor
  • DNA, Catalytic/metabolism
  • Animals
  • Receptor, ErbB-2/metabolism
  • Interferon Regulatory Factor-1/metabolism
  • Reactive Oxygen Species/metabolism
  • Mice
  • DNA Repair
  • DNA Damage
  • Glutathione/metabolism
  • Nucleic Acids/metabolism

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