Cell-Penetrating Cross-β Peptide Assemblies with Controlled Biodegradable Properties.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Chemical Biology

Background:

• Self-assembled peptide nanostructures (SPNs) are promising biomaterials.
• A key limitation of conventional SPNs is the slow hydrolysis rate of amide bonds, hindering their degradation.
• Developing SPNs with tunable biodegradation is crucial for biomedical applications.

Purpose of the Study:

• To engineer cell-penetrating cross-β SPNs with controllable biodegradation rates.
• To design self-assembling depsipeptides (SADPs) that incorporate hydrolyzable ester bonds.
• To create versatile nanostructures for biomedical applications.

Main Methods:

• Designed self-assembling β-sheet peptides incorporating ester bonds (SADPs) to form 1D fibers.
• Controlled hydrolysis rates by adjusting pH, temperature, and ester unit structure.
• Conjugated cell-penetrating peptide segments to SADP segments to form 3D vesicle-like structures.
• Assessed cell internalization and intracellular degradation of the nanostructures.

Main Results:

• SADPs self-assembled into bilayer β-sandwich 1D fibers, similar to conventional SPNs.
• Hydrolysis rates were successfully modulated by environmental factors and ester structure.
• Attachment of cell-penetrating peptides induced transformation into 3D vesicle-like nanostructures.
• Demonstrated efficient cellular uptake and subsequent intracellular degradation of the 3D nanostructures.

Conclusions:

• Developed biodegradable cross-β SPNs with tunable hydrolysis rates.
• Engineered cell-penetrating 3D nanostructures from SADPs with controlled degradation.
• Provided a valuable toolkit for designing advanced self-assembling peptide biomaterials.