Polycation-telodendrimer nanocomplexes for intracellular protein delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Cationic polymers are promising for intracellular protein delivery but suffer from poor stability, high cytotoxicity, and non-specific cell uptake.
• These limitations hinder their clinical application for protein therapeutics.

Purpose of the Study:

• To develop a facile strategy to optimize protein-polycation complexes for enhanced intracellular delivery.
• To overcome the limitations of traditional polycationic vectors.

Main Methods:

• Encapsulation of protein-polycation complexes using linear-dendritic telodendrimers.
• Utilizing multivalent and hybrid supramolecular interactions for nanoparticle formation.
• Characterization of nanoparticle size, cytotoxicity, and cellular uptake.

Main Results:

• Formation of sub-20 nm nanoparticles with improved stability.
• Significant reduction in polycation-associated cytotoxicity and hemolytic activity.
• Elimination of polycation aggregation and non-specific binding to biomacromolecules.
• Demonstrated dissociation of telodendrimers during cellular uptake, restoring polycation delivery capability.

Conclusions:

• Telodendrimers provide a versatile platform for rational design and functional integration in nanoparticle formulation.
• This strategy effectively addresses the key challenges associated with polycationic vectors for intracellular protein delivery.
• The developed method offers a promising approach for advancing the delivery of protein therapeutics.