Nanofiber Polyplex Formation Based on the Morphology Elongation by the Intrapolyplex PEG Crowding Effect.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gene Delivery Systems

Background:

• Polyplexes formed by cationic polymers and plasmid DNA (pDNA) are crucial for gene delivery.
• Controlling polyplex morphology and stability is essential for efficient gene delivery and expression.

Purpose of the Study:

• To investigate the impact of multiarm poly(ethylene glycol)-poly(l-lysine) (maPEG-PLL) architecture, specifically maPEG head size, on polyplex formation with pDNA.
• To evaluate how maPEG crowding influences polyplex morphology and gene silencing efficacy.

Main Methods:

• Synthesis of maPEG-PLL block copolymers with varying maPEG head sizes.
• Confirmation of polyplex formation using gel retardation assays.
• Morphological analysis of polyplexes under different maPEG head sizes.
• Assessment of cell-free gene expression inhibition.

Main Results:

• maPEG-PLL demonstrated noncooperative polyplex formation, indicating effective polyplex hydration.
• Increased maPEG head size led to polyplex elongation from spheres to nanorods and nanofibers due to intrapolyplex PEG crowding.
• Larger maPEG heads improved inhibition of cell-free gene expression decrease.

Conclusions:

• The size of the maPEG head in maPEG-PLL copolymers significantly influences polyplex morphology and gene delivery efficiency.
• Controlling pDNA packaging through polymer architecture is critical for optimizing gene silencing and delivery outcomes.
• maPEG crowding is a key factor in dictating polyplex shape and function.