Externally Triggered Activation of Nanostructure-Masked Cell-Penetrating Peptides

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Cell-penetrating peptides (CPPs) are valuable for intracellular delivery but suffer from non-specific uptake and cytotoxicity.
• Current delivery methods lack precise spatial and temporal control, hindering clinical applications of CPPs.

Purpose of the Study:

• To develop a cold atmospheric plasma-responsive delivery platform for transiently suppressing and externally activating peptide membrane activity.
• To engineer a DNA-based nanostructure for controlled intracellular delivery of therapeutic peptides.

Main Methods:

• Fabrication of DNA nanoflower nanostructures (150-250 nm) for complexing peptides.
• Utilizing cold atmospheric plasma to trigger the disruption of DNA masking and restore peptide function.
• Assessing system inertness under physiological conditions and activation kinetics via plasma treatment.
• Evaluating controlled peptide activity using fluorescence recovery, cellular uptake assays, and cytotoxicity measurements in 2D and 3D models.

Main Results:

• The DNA nanoflower system demonstrated inertness under physiological conditions and rapid activation upon plasma exposure.
• Precise spatial and temporal control of peptide activity was achieved in both monolayer and 3D spheroid models.
• The platform successfully regulated peptide function without biochemical triggers or permanent modifications.

Conclusions:

• The developed externally activatable nanomaterial platform enables precise control over peptide function for therapeutic applications.
• This modular strategy offers a promising approach for developing peptide therapeutics requiring controlled activation in complex biological environments.
• The system overcomes limitations of non-specific uptake and off-target cytotoxicity associated with traditional cell-penetrating peptides.