A1 Refereed original research article in a scientific journal
Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy
Authors: Yan Jiaqi, Bhadane Rajendra, Ran Meixin, Ma Xiaodong, Li Yuanqiang, Zheng Dongdong, Salo-Ahen Outi M. H., Zhang Hongbo
Publisher: Springer Nature
Publication year: 2024
Journal: Nature Communications
Journal name in source: Nature communications
Journal acronym: Nat Commun
Article number: 3684
Volume: 15
Issue: 1
ISSN: 2041-1723
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-024-48149-9(external)
Web address : https://www.nature.com/articles/s41467-024-48149-9(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/393446413(external)
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 Ca2+/(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.
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