Polymers modified with double-tailed fluorous compounds for efficient DNA and siRNA delivery.

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Gene Delivery Systems

Background:

• Cationic polymers are common gene carriers but suffer from low transfection efficiency and toxicity.
• Fluorination enhances gene delivery performance but typically requires high fluorous chain density.
• A need exists for efficient and less toxic fluorinated gene delivery vectors.

Purpose of the Study:

• To develop a novel strategy for creating fluorinated polymers with minimal fluorous chains for enhanced DNA and siRNA delivery.
• To synthesize and characterize novel fluorinated polymers by conjugating a fluorous compound to dendrimers and polyethylenimine.
• To evaluate the transfection efficacy and toxicity of these novel polymers.

Main Methods:

• A double-tailed fluorous compound, 2-chloro-4,6-bis[(perfluorohexyl)propyloxy]-1,3,5-triazine (CBT), was synthesized.
• CBT was conjugated onto dendrimers of varying generations and low molecular weight polyethylenimine.
• The transfection efficacy of the resulting polymers for EGFP, luciferase, and siRNA was assessed in vitro and in vivo, alongside toxicity evaluations.

Main Results:

• Synthesized polymers with 1-2 conjugated CBT moieties demonstrated significantly improved DNA transfection efficacy compared to unmodified polymers.
• The modified polymers exhibited high efficacy for siRNA delivery across different cell lines.
• Generation 1 dendrimer modified with 1.9 CBT moieties (G1-CBT1.9) showed the highest efficacy, comparable to Lipofectamine 2000, and demonstrated effective in vivo gene silencing.
• All CBT-modified polymers displayed minimal toxicity at optimal transfection conditions.

Conclusions:

• A facile synthesis strategy was established for constructing efficient fluorinated polymers with minimal fluorous chains.
• The developed fluorinated polymers, particularly G1-CBT1.9, represent promising non-viral vectors for both DNA and siRNA delivery.
• This approach offers a viable route to design advanced, low-toxicity gene delivery systems.