Rationally designed peptide nanosponges for cell-based cancer therapy

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Biomaterials Engineering

Background:

• Supramolecular aggregates offer unique properties for various applications.
• Designing building blocks with specific geometries is key to controlling self-assembly.
• Peptide sequences can be incorporated to impart specific functionalities.

Purpose of the Study:

• To synthesize and characterize a novel type of supramolecular aggregate, termed "nanosponge."
• To investigate the self-assembly behavior of cholesterol-peptide-trimaleimide building blocks.
• To explore the structural and toxicological properties of the newly formed nanosponges.

Main Methods:

• Synthesis of cholesterol-(K/D)nDEVDGC)3-trimaleimide building blocks via Michael addition.
• Self-assembly studies in aqueous buffer to form nanosponges.
• Molecular dynamics (MD) simulations (explicit solvent and coarse-grained) for structural analysis.
• In vitro cytotoxicity assays using monocyte/macrophage-like cells.

Main Results:

• Stable nanosponges were formed from cholesterol-(K)nDEVDGC)3-trimaleimides and 1:1 mixtures with cholesterol-(K/D)nDEVDGC)3-trimaleimides.
• Cholesterol-(D)nDEVDGC)3-trimaleimide alone did not form supramolecular aggregates.
• Nanosponges exhibited diameters ranging from 80 nm to several micrometers.
• The synthesized nanosponges demonstrated virtual non-toxicity to tested cell lines.

Conclusions:

• Novel trigonal supramolecular building blocks can self-assemble into stable nanosponges.
• The peptide sequence (K vs. D) and mixing ratios are critical for nanosponge formation.
• The characterized nanosponges possess favorable structural and safety profiles for potential biomaterial applications.