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

Author

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  • Jiaqi Yan

    (Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road
    Åbo Akademi University
    University of Turku and Åbo Akademi University)

  • Rajendra Bhadane

    (Åbo Akademi University
    University of Turku
    Åbo Akademi University)

  • Meixin Ran

    (Åbo Akademi University
    University of Turku and Åbo Akademi University)

  • Xiaodong Ma

    (Åbo Akademi University
    University of Turku and Åbo Akademi University)

  • Yuanqiang Li

    (Åbo Akademi University
    University of Turku and Åbo Akademi University)

  • Dongdong Zheng

    (Fudan University Shanghai Cancer Center)

  • Outi M. H. Salo-Ahen

    (Åbo Akademi University
    Åbo Akademi University)

  • Hongbo Zhang

    (Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road
    Åbo Akademi University
    University of Turku and Åbo Akademi University)

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 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.

Suggested Citation

  • Jiaqi Yan & Rajendra Bhadane & Meixin Ran & Xiaodong Ma & Yuanqiang Li & Dongdong Zheng & Outi M. H. Salo-Ahen & Hongbo Zhang, 2024. "Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48149-9
    DOI: 10.1038/s41467-024-48149-9
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    References listed on IDEAS

    as
    1. Angelika Schmalzl & Tamara Leupold & Lucas Kreiss & Maximilian Waldner & Sebastian Schürmann & Markus F. Neurath & Christoph Becker & Stefan Wirtz, 2022. "Interferon regulatory factor 1 (IRF-1) promotes intestinal group 3 innate lymphoid responses during Citrobacter rodentium infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Roopesh Anand & Erika Buechelmaier & Ondrej Belan & Matthew Newton & Aleksandra Vancevska & Artur Kaczmarczyk & Tohru Takaki & David S. Rueda & Simon N. Powell & Simon J. Boulton, 2022. "HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51," Nature, Nature, vol. 601(7892), pages 268-273, January.
    3. Joost van Mameren & Mauro Modesti & Roland Kanaar & Claire Wyman & Erwin J. G. Peterman & Gijs J. L. Wuite, 2009. "Counting RAD51 proteins disassembling from nucleoprotein filaments under tension," Nature, Nature, vol. 457(7230), pages 745-748, February.
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