Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Drug Delivery Systems

Background:

• Cancer poses a significant global health challenge, with tumor microenvironments hindering therapeutic access and causing recurrence.
• Cell-penetrating peptides (CPPs) facilitate molecular transport across cell membranes but often suffer from poor proteolytic stability, limiting their therapeutic potential.
• Developing CPPs with enhanced stability and penetration capabilities is crucial for improving drug delivery efficiency.

Purpose of the Study:

• To describe a protocol for synthesizing fluorescently labeled cyclic and linear polyarginine R8 peptides.
• To investigate the cell permeability of these cyclic and linear CPPs.
• To advance the development of novel molecular transporters for biomedical applications.

Main Methods:

• Synthesis of fluorescently labeled cyclic and linear polyarginine R8 peptides.
• Characterization of peptide stability and membrane translocation properties.
• Assessment of cell permeability using established assays.

Main Results:

• Cyclic CPPs demonstrated superior permeability in cancer cells and tissues compared to linear counterparts.
• The synthesized cyclic polyarginine R8 peptide exhibited enhanced proteolytic stability.
• Key steps for investigating CPP cell permeability were established.

Conclusions:

• Cyclic CPPs represent a promising strategy for overcoming biological barriers in drug delivery.
• The developed cyclic polyarginine R8 peptide shows potential as an efficient molecular transporter.
• This work provides a foundation for further development of stable and permeable CPPs for cancer therapy.