Polymerized spermine as a novel polycationic nucleic acid carrier system.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Spermine is a natural DNA-condensing agent.
• Developing efficient and safe nucleic acid carriers is crucial for gene therapy.
• Polycationic polymers offer potential for nucleic acid delivery.

Purpose of the Study:

• To synthesize and characterize novel polyspermine-based cationic polymers.
• To evaluate their potential as nucleic acid carriers for gene and siRNA delivery.
• To investigate the impact of linker molecules on polymer properties and transfection efficacy.

Main Methods:

• Spermine was condensed with bischloroformate, succinyl chloride, and glyoxal to form polyspermine carbamate (PSP-Carb), polyspermine amide (PSP-Amide), and polyspermine imine (PSP-Imine).
• Degradability, cytotoxicity (using COS-7 and HepG2 cells), nucleic acid condensation, and transfection efficiency (luciferase plasmid and siRNA) were assessed.
• Nanoparticle formation and zeta potential were measured using dynamic light scattering.

Main Results:

• PSP-Carb and PSP-Amide demonstrated long-term stability (half-life > 2 months), while PSP-Imine had a shorter half-life (11h).
• Cytotoxicity varied, with PSP-Carb > PSP-Amide > PSP-Imine.
• All polymers condensed DNA into nanoparticles (150-200 nm) with positive zeta potentials (+15-30 mV).
• Transfection efficiency was similar in COS-7 cells, but PSP-Carb was superior in HepG2 cells; PSP-Amide showed higher gene silencing in COS-7 cells.

Conclusions:

• Polyspermine-based polymers can effectively condense nucleic acids into nanoparticles for gene delivery.
• Linker structure significantly influences polymer stability, cytotoxicity, and transfection/silencing efficacy.
• PSP-Carb and PSP-Amide show promise as stable and effective nucleic acid carriers, particularly for specific cell types.