Gene delivery to neuroblastoma cells by poly (l-lysine)-grafted low molecular weight polyethylenimine copolymers.
Polyethylenimine (PEI) and poly (l-lysine) (PLL) are among the most investigated non-viral gene carriers. However, both polymers contain deficiencies that restrict their applications. In the present study, we synthesized PLL-alkyl-PEI conjugates via 6-carbon alkyl linker and investigated their possible advantages in gene delivery. Four PLL copolymers were synthesized with different molecular weights and ratios of PEI. The physiochemical properties of synthesized conjugates such as size, zeta potential, DNA condensation ability, buffering capacity and cytotoxicity were investigated. Renilla luciferase assay was employed to evaluate the gene transfection efficiency of pDNA-polymer to Neuro2A cell line. DNA condensation and particle size measurements showed that new PLL-PEI conjugates could form polyplexes in nano-scale size in the range of 99-122 nm and were able to condense DNA at low concentration. While cytotoxicity reduced in some groups, the transfection efficiency increased about 2.8 and 4 fold as compared to the unmodified PEI 1.8 kDa and 10 kDa, respectively. The results of the present study showed that the chemical modifications of PEI with PLL could significantly improve transfection efficiency and PLP10-10% shows the most promise as a new gene carrier.
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Askarians891@mums.ac.ir.
Saeedeh
S
Askarian
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Abnouskh@mums.ac.ir.
Khalil
K
Abnous
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: DarroudiM@mums.ac.ir.
Majid
M
Darroudi
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Oskueekr@mums.ac.ir.
Reza Kazemi
RK
Oskuee
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Ramezanim@mums.ac.ir.
Mohammad
M
Ramezani
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D015203:Reproducibility of Results; D014162:Transfection / Q000379:methods*
D011107:Polylysine; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases
Cytotoxicity; Gene delivery; Nanoparticles; Non-viral vector; Poly (l-lysine); Polyethylenimine