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.
Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Zixiu
Z
Du
Moying
M
Chen
Qianqian
Q
He
Yi
Y
Zhou
Tuo
T
Jin
D000577:Amides / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D002219:Carbamates / Q000737:chemistry; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage*; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006207:Half-Life; D056945:Hep G2 Cells; D006801:Humans; D007097:Imines / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D013096:Spermine / Q000737:chemistry*; D014162:Transfection
D000577:Amides; D002219:Carbamates; D002412:Cations; D007097:Imines; D011108:Polymers; D034741:RNA, Small Interfering; D013096:Spermine; D004247:DNA