Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Polyethylenimine (PEI) is a common non-viral gene delivery vector.
• PEI exhibits cytotoxicity and limited serum stability, hindering its clinical application.
• Developing novel PEI-based polymers with improved properties is crucial for effective gene delivery.

Purpose of the Study:

• To synthesize and characterize novel oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers.
• To evaluate the gene delivery efficiency, cytotoxicity, and transfection mechanism of SP2K polymers.
• To investigate the potential of SP2K polymers as advanced gene delivery systems.

Main Methods:

• Reductive amination was used to crosslink periodate-oxidized sucrose with polyethylenimine 2K (PEI2K).
• Synthesis was confirmed using ¹H NMR and FTIR spectroscopy.
• Polyplex formation, zeta potential, particle size, cytotoxicity, transfection efficiency, and cellular uptake pathways were analyzed.

Main Results:

• SP2K polymers formed stable, nano-sized polyplexes with plasmid DNA (pDNA).
• SP2K polymers showed lower cytotoxicity than PEI25K and exhibited higher transfection efficiency in both serum and serum-free conditions.
• SP2K polymers possess high osmolality and endosome buffering capacity, facilitating efficient endosomal escape via multiple pathways, including caveolae-mediated endocytosis.

Conclusions:

• Oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers are effective non-viral gene delivery vectors.
• SP2K polymers demonstrate superior gene delivery efficiency and serum stability compared to PEI25K.
• The high osmolality and endosome buffering capacity of SP2K polymers contribute to their efficient transfection mechanism.