Unlocking intracellular targets: Smart multistage-responsive polyionic vesicular platforms for advancing...

Area of Science:

• Biotechnology and Biomedical Engineering
• Drug Delivery Systems
• Nanomedicine

Background:

• Protein drugs face challenges crossing cellular membranes due to their intrinsic properties.
• This limits their use in regulating intracellular biological processes.

Purpose of the Study:

• To develop a novel platform for efficient intracellular protein delivery.
• To overcome biological barriers for enhanced therapeutic efficacy.

Main Methods:

• Engineered biodegradable poly(amino acid) polyion complex vesicles (PICsomes).
• Functionalized PICsomes with RGD-targeting ligands for enhanced cellular uptake.
• Investigated pH and redox responsiveness for controlled intracellular release.

Main Results:

• PICsomes successfully encapsulated diverse proteins.
• Demonstrated efficacy in preclinical models of tumors and atherosclerosis.
• Targeted accumulation and enhanced cellular internalization via RGD ligands and endocytosis.
• Stimuli-responsive release of proteins within target subcellular compartments.

Conclusions:

• The developed PICsomes platform offers a promising strategy for intracellular protein delivery.
• This approach enhances therapeutic potential by enabling effective engagement with intracellular targets.
• Represents a generalizable method for expanding the scope of protein-based therapeutics.