Polymerized spermine as a novel polycationic nucleic acid carrier system.

Spermine, an endogenous amino-group bearing monomer that condenses DNA in sperm, was used as the basic building block to form polycationic nucleic acid carriers via condensation with one of three linker molecules - bischloroformate, succinyl chloride, and glyoxal. The three cationic polymers, polyspermine carbamate (PSP-Carb), polyspermine amide (PSP-Amide) and polyspermine imine (PSP-Imine) were examined for their degradability, cytotoxicity, ability to condense nucleic acids to nanoparticles, and ability to transfect genes or siRNA to cells. PSP-Carb and PSP-Amide exhibited a half-life of more than 2 months when incubated in aqueous buffers at 37°C, while the half-life of PSP-Imine was 11h. Relative cytotoxicity of the polymers, as measured by COS-7 and HepG2 cell viability, was in the order of PSP-Carb>PSP-Amide>PSP-Imine. Each cationic polymer condensed the luciferase plasmid to nanoparticles of 150-200 nm diameters and with a zeta potential of +15-30 mV when the mass ratio of polymer-to-DNA was over 8/1. The three polycationic carriers showed similar luciferase transfection activity in COS-7 cells, while the transfection efficiency of PSP-Carb was significantly higher than that of the other two in HepG2 cells. PSP-Amide exhibited significantly higher gene silencing activity in COS-7 cells, suggesting the linkage structures play an important role in the activity of the polyspermine-based nucleic acid carriers.