适体
脱氧核酶
核酸
癌症
癌症治疗
核酶
癌症研究
计算生物学
医学
化学
DNA
核糖核酸
生物
生物化学
遗传学
内科学
基因
作者
Jiaqi Yan,Rajendra Bhadane,Meixin Ran,Xiaodong Ma,Yuanqiang Li,Dongdong Zheng,Outi M. H. Salo‐Ahen,Hongbo Zhang
标识
DOI:10.1038/s41467-024-48149-9
摘要
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.
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