Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene delivery.Eight new spermine-based protonatable surfactants were designed,sy...Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene delivery.Eight new spermine-based protonatable surfactants were designed,synthesized and evaluated as non-viral pH-sensitive gene carriers.These carriers formed stable complexes with plasmid DNA at an N/P ratio as low as 2.The sizes of the carrier/pDNA nanoparticles (N/P = 12) were in the range of 90–130 nm,smaller than that of Lipofectamine2000/pDNA nanoparticles.The pDNA nanoparticles of the carriers exhibited substantially increased hemolysis when pH decreased from 7.4 to 5.5.The DNA nanoparticles had low cytotocixity,similar to that of Lipofectamine-2000/pDNA nanoparticles.The pH-sensitive gene carriers with no helper lipids resulted in much higher intracellular transfection and gene expression in U87 cells than Lipofectamine-2000.[N,N′-Bis(oleoylcysteinyl)(β-alanyl-α-lysyl)]-spermine monoamide (SKACO) resulted in the highest luciferase transfection efficiency,more than 400 times higher than that of Lipofectamine-2000,and GFP expression in 71% of transfected U87 cells.SKACO was identified as a promising lead carrier for efficient gene delivery.These spermine-based pH-sensitive amphiphilic carriers have a potential to be further developed as efficient non-viral multifunctional gene delivery systems.展开更多
The design and development of safe and effective multifunctional siRNA delivery systems are critical for clinical application of RNAi therapeutics. Here we evaluated eight new spermine-based surfactant multifunctional...The design and development of safe and effective multifunctional siRNA delivery systems are critical for clinical application of RNAi therapeutics. Here we evaluated eight new spermine-based surfactant multifunctional carriers for siRNA delivery. These carriers complexed with siRNA forming stable compact nanoparticles with sizes around 100 nm. The multifunctional carriers mediated higher intracellular siRNA transfection than Lipofectamine-2000. The siRNA nanoparticles of the multifunctional carriers exhibited low cytotoxicity as shown by MTT assay. Three of the eight multifunctional carriers showed higher silencing efficiency than Lipofectamine-2000 in both U87-Luc cells and CHO-GFP cells. SKAHCO showed the highest siRNA delivery efficiency among the carriers. It resulted in 84.6±5.5% silencing of luciferase activity in U87-Luc cells, much higher than that (62.8± 3.4%) from Lipofectamine-2000. In conclusion, the spermine based multifunctional carriers are promising for highly efficient intracellular siRNA delivery.展开更多
文摘Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene delivery.Eight new spermine-based protonatable surfactants were designed,synthesized and evaluated as non-viral pH-sensitive gene carriers.These carriers formed stable complexes with plasmid DNA at an N/P ratio as low as 2.The sizes of the carrier/pDNA nanoparticles (N/P = 12) were in the range of 90–130 nm,smaller than that of Lipofectamine2000/pDNA nanoparticles.The pDNA nanoparticles of the carriers exhibited substantially increased hemolysis when pH decreased from 7.4 to 5.5.The DNA nanoparticles had low cytotocixity,similar to that of Lipofectamine-2000/pDNA nanoparticles.The pH-sensitive gene carriers with no helper lipids resulted in much higher intracellular transfection and gene expression in U87 cells than Lipofectamine-2000.[N,N′-Bis(oleoylcysteinyl)(β-alanyl-α-lysyl)]-spermine monoamide (SKACO) resulted in the highest luciferase transfection efficiency,more than 400 times higher than that of Lipofectamine-2000,and GFP expression in 71% of transfected U87 cells.SKACO was identified as a promising lead carrier for efficient gene delivery.These spermine-based pH-sensitive amphiphilic carriers have a potential to be further developed as efficient non-viral multifunctional gene delivery systems.
文摘The design and development of safe and effective multifunctional siRNA delivery systems are critical for clinical application of RNAi therapeutics. Here we evaluated eight new spermine-based surfactant multifunctional carriers for siRNA delivery. These carriers complexed with siRNA forming stable compact nanoparticles with sizes around 100 nm. The multifunctional carriers mediated higher intracellular siRNA transfection than Lipofectamine-2000. The siRNA nanoparticles of the multifunctional carriers exhibited low cytotoxicity as shown by MTT assay. Three of the eight multifunctional carriers showed higher silencing efficiency than Lipofectamine-2000 in both U87-Luc cells and CHO-GFP cells. SKAHCO showed the highest siRNA delivery efficiency among the carriers. It resulted in 84.6±5.5% silencing of luciferase activity in U87-Luc cells, much higher than that (62.8± 3.4%) from Lipofectamine-2000. In conclusion, the spermine based multifunctional carriers are promising for highly efficient intracellular siRNA delivery.
