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

Ryuta Aono¹, Eiji Yuba¹, Atsushi Harada¹

¹Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.

ACS Macro Letters

|May 20, 2022

Summary

We developed a multiarm poly(ethylene glycol)-poly(l-lysine) block copolymer (maPEG-PLL) to study polyplex formation. Increasing the maPEG head size alters polyplex shape and enhances gene expression, highlighting packaging control importance.

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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.