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DNA mechanocapsules for programmable piconewton responsive drug delivery
Arventh Velusamy1, Radhika Sharma1, Sk Aysha Rashid1
1Department of Chemistry, Emory University, Atlanta, GA, USA.
Nature Communications
|January 24, 2024
Summary
Scientists developed DNA mechanocapsules (DMCs) that release drugs when cells apply force. These force-responsive capsules target cellular mechanical phenotypes for potential applications in disease treatment.
Area of Science:
- Biophysics
- Nanotechnology
- Molecular Biology
Background:
- Cellular mechanical dysregulation is linked to diseases like fibrosis and cancer.
- Targeting drugs based on a cell's mechanical properties is a promising therapeutic strategy.
Purpose of the Study:
- To develop force-responsive DNA mechanocapsules (DMCs) for targeted drug delivery.
- To investigate the mechanical response and cargo release mechanisms of DMCs.
Main Methods:
- Designed DNA tetrahedrons forming force-responsive DMCs.
- Utilized computational modeling to predict force-induced rupture.
- Functionalized DMCs with adhesion ligands for cell interaction.
- Encapsulated macromolecular cargos (dextran, oligonucleotide drugs).
- Validated force-induced release and uptake via flow cytometry.
- Demonstrated mRNA knockdown of HIF-1α based on cellular traction forces.
Main Results:
- DMCs exhibit force-responsive rupture, tunable by force application.
- Functionalized DMCs denature upon interaction with cell receptors.
- DMCs effectively encapsulate cargo with minimal leakage and high nuclease resistance.
- Force-induced cargo release and cellular uptake were confirmed.
- Targeted mRNA knockdown was achieved, dependent on cellular force magnitude.
Conclusions:
- DNA mechanocapsules offer a novel platform for targeting cellular biophysical phenotypes.
- DMCs demonstrate potential for precise drug delivery in diseases driven by mechanical alterations.
- Applications in immunology and cancer biology are anticipated.
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