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

Jiaqi Yan, Rajendra Bhadane, Meixin Ran, Xiaodong Ma, Yuanqiang Li, Dongdong Zheng, Outi M H Salo-Ahen, Hongbo Zhang*

*Korresponderande författare för detta arbete

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

26 Citeringar (Scopus)
17 Nedladdningar (Pure)

Sammanfattning

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.

OriginalspråkEngelska
Artikelnummer3684
Antal sidor20
TidskriftNature Communications
Volym15
DOI
StatusPublicerad - 1 maj 2024
MoE-publikationstypA1 Tidskriftsartikel-refererad

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