Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery

Area of Science:

• Biomaterials Science
• Gene Delivery Systems
• Polymer Chemistry

Background:

• Successful gene delivery relies on efficient endosomal escape and intracellular release.
• Acid-labile polymer units aid endosomal escape, while reducible units facilitate intracellular release.
• Existing carriers like polyethylenimine (PEI) face limitations in efficiency and biocompatibility.

Purpose of the Study:

• To synthesize and evaluate dual-responsive poly(amido amine)s for improved gene delivery.
• To compare the gene transfection efficiency and cytotoxicity of dual-responsive polymers against single-responsive counterparts and PEI.

Main Methods:

• Synthesis of poly(amido amine)s incorporating both acid-labile and bioreducible functionalities.
• Formation of DNA/polymer complexes (polyplexes).
• Evaluation of gene transfection efficiency and cytotoxicity in three distinct cell lines.

Main Results:

• Polyplexes formed with dual-responsive polymers demonstrated significantly higher gene transfection efficiency.
• Dual-responsive polymers exhibited markedly lower cytotoxicity compared to polyethylenimine (tens of times less).
• Performance surpassed that of single-responsive polymer carriers.

Conclusions:

• Polymers possessing both reducible and acid-labile properties represent a promising strategy for advanced gene delivery.
• These dual-responsive materials offer a pathway to achieve both high transfection efficiency and enhanced biocompatibility.
• The developed poly(amido amine)s show potential as effective and safe non-viral gene vectors.