Engineering Protein-Based Lipid-Binding Nanovesicles via Catechol-Amine-Derived Coacervation with Their Underlying...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Surface Chemistry

Background:

• Nonphospholipid nanovesicles offer advantages over traditional liposomes, with protein/peptide-based versions showing reduced immunogenicity and enhanced bioactivity.
• Understanding protein-lipid and protein-membrane interactions is crucial for developing effective nanovesicle delivery systems.
• Current knowledge gaps exist regarding the fundamental mechanisms governing these interactions.

Purpose of the Study:

• To engineer protamine-based nonphospholipid nanovesicles by modulating intramolecular catechol-amine interactions.
• To investigate the impact of grafting catechol (CA) and trihydroxybenzene (GA) groups onto protamine (Prot) on vesicle formation and properties.
• To elucidate the role of iron(III) ions (Fe3+) in enhancing nanovesicle-lipid interactions and cell membrane interactions.

Main Methods:

• Protamine was modified with catechol (CA) and trihydroxybenzene (GA) groups.
• Salt-triggered coacervation in an alkaline environment was used to form nanovesicles (200-1200 nm).
• Lipid bubble force measurements and surface charge difference mapping were employed to study nanomechanics and cell interactions.

Main Results:

• Protamine-based nanovesicles were successfully engineered with tunable sizes.
• Bonding affinity to lipid interfaces increased with catechol modification and Fe3+ addition (Prot-CA-Fe3+ > Prot-CA > Prot).
• Trace Fe3+ significantly enhanced nanovesicle-lipid interactions through catechol-amine and Fe3+-complexation synergy, improving interactions with human gingival fibroblasts.

Conclusions:

• Intramolecular catechol-amine interactions provide an effective strategy for engineering protein-based nanovesicles.
• Iron ion complexation can significantly enhance the interaction of these nanovesicles with lipid interfaces and cell membranes.
• This study offers valuable insights into nanovesicle-cell membrane interactions and a paradigm for modulating targeted delivery.