Charge-conversional polyionic complex micelles-efficient nanocarriers for protein delivery into cytoplasm

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Cytoplasmic protein delivery faces challenges with endosomal entrapment.
• Polyionic complex (PIC) micelles offer potential for intracellular cargo transport.
• Charge-conversion strategies are being explored to improve endosomal release.

Purpose of the Study:

• To develop novel PIC micelles for efficient cytoplasmic protein delivery.
• To investigate the role of charge-conversional moieties in PIC micelle stability and endosomal release.
• To assess the efficacy of these PIC micelles in releasing protein cargo into the cytoplasm.

Main Methods:

• Synthesis of PIC micelles incorporating citaconic amide or cis-aconitic amide moieties.
• Characterization of PIC micelle stability with varying protein cargo charge densities.
• Evaluation of endosomal pH-triggered charge-conversion and micelle dissociation.
• Assessment of endosomal release efficiency and cytoplasmic protein delivery.

Main Results:

• PIC micelles with citaconic amide or cis-aconitic amide demonstrated stability with increased protein cargo charge density.
• Charge-conversion of the moieties within endosomes induced PIC micelle dissociation.
• Efficient endosomal release of protein cargo was achieved without the need for cross-linking.

Conclusions:

• Developed PIC micelles provide a stable platform for protein delivery.
• Charge-conversion is an effective strategy for triggering endosomal release and enhancing cytoplasmic delivery.
• This approach offers a promising non-crosslinking method for intracellular protein delivery.