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DNA mechanocapsules for programmable piconewton responsive drug delivery

Author

Listed:
  • Arventh Velusamy

    (Emory University)

  • Radhika Sharma

    (Emory University)

  • Sk Aysha Rashid

    (Emory University)

  • Hiroaki Ogasawara

    (Emory University)

  • Khalid Salaita

    (Emory University
    Georgia Institute of Technology and Emory University)

Abstract

The mechanical dysregulation of cells is associated with a number of disease states, that spans from fibrosis to tumorigenesis. Hence, it is highly desirable to develop strategies to deliver drugs based on the “mechanical phenotype” of a cell. To achieve this goal, we report the development of DNA mechanocapsules (DMC) comprised of DNA tetrahedrons that are force responsive. Modeling shows the trajectory of force-induced DMC rupture and predicts how applied force spatial position and orientation tunes the force-response threshold. DMCs functionalized with adhesion ligands mechanically denature in vitro as a result of cell receptor forces. DMCs are designed to encapsulate macromolecular cargos such as dextran and oligonucleotide drugs with minimal cargo leakage and high nuclease resistance. Force-induced release and uptake of DMC cargo is validated using flow cytometry. Finally, we demonstrate force-induced mRNA knockdown of HIF-1α in a manner that is dependent on the magnitude of cellular traction forces. These results show that DMCs can be effectively used to target biophysical phenotypes which may find useful applications in immunology and cancer biology.

Suggested Citation

  • Arventh Velusamy & Radhika Sharma & Sk Aysha Rashid & Hiroaki Ogasawara & Khalid Salaita, 2024. "DNA mechanocapsules for programmable piconewton responsive drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44061-w
    DOI: 10.1038/s41467-023-44061-w
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    References listed on IDEAS

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    1. Ion Andreu & Bryan Falcones & Sebastian Hurst & Nimesh Chahare & Xarxa Quiroga & Anabel-Lise Roux & Zanetta Kechagia & Amy E. M. Beedle & Alberto Elosegui-Artola & Xavier Trepat & Ramon Farré & Timo B, 2021. "The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Pontus Nordenfelt & Hunter L. Elliott & Timothy A. Springer, 2016. "Coordinated integrin activation by actin-dependent force during T-cell migration," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    3. Yun Zhang & Chenghao Ge & Cheng Zhu & Khalid Salaita, 2014. "DNA-based digital tension probes reveal integrin forces during early cell adhesion," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
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