Biodegradable cationic polymers with lower transfection cytotoxicity

4591 A major problem involving cell transfection using current cationic polymer gene carriers is the relative high cytotoxicity encountered while approaching the desired transfection efficiency. To overcome this problem, a biodegradable cationic polymer library was constructed by a parallel chemical synthesis method which varied the structure and molecular size. High throughput transfection screening assays (GFP, Luciferase, and MTT) were used in combination with GPC and NMR to study the relationship between polymer size, structure, transfection efficiency, and cytotoxicity. Human transformed cells (HEK 293) and primary cells (HUVEC cells) were used in this study. Several of the best candidates were selected from the samples screened. The results showed that the novel biodegradable cationic polymers had significantly improved the transfection performances in HEK 293 cells (0%-10% cytotoxicity at 93%-98% transfection efficiency) compared to the most common polymer transfection reagent, JetPEI™ (10-25% cytotoxicity at 85%-92% transfection efficiency) and SuperFect (12%-30% cytotoxicity at 85%-90% transfection efficiency). Using human umbilical vascular endothelial primary cells (HUVEC), the biodegradable cationic polymers showed dramatically higher transfection efficiencies (60%) with low cytotoxicities (20% to 30%) compared to JetPEI™ (10% transfection efficiency and 50% cytotoxicity) and SuperFect™ (8% transfection efficiency and 60% cytotoxicity). The results indicated that the biodegradable polymers are useful reagents for reducing transfection cytotoxicities while attaining high transfection efficiencies when used for in vitro applications. These biodegradable polymers may also prove to be useful tools for gene delivery for in vivo applications.