title: The intracellular delivery of plasmid DNA using cationic reducible carbon nanotube - Disulfide conjugates of polyethylenimine.
abstract: A series of polyethylenimine conjugates of single-walled carbon nanotube (PEI-SWNT) containing bioreducible disulfide bonds was synthesized and evaluated for their transfection efficiency. Different molecular weights of polyethylenimine (PEI) were thiolated with different mole ratio of 2-iminothiolane (2-IT). Single-walled carbon nanotube (SWNT) was first carboxylated and then three different cysteine-functionalized SWNT formulations were synthesized via introduced linkers: a) carbonyl group b) spermidine c) 1,8-diamino 3,6-dioxo octane. The final nanocarriers were fabricated upon conjugation of thiolated PEIs and thiolated SWNT via oxidative disulfide bond formation. All PEI-disulfide-SWNT conjugates were capable of DNA condensation and showed improved viability and transfection efficiency compared to PEI itself. Transfection efficiencies were up to 1500 times greater than PEI 25kDa (C/P=0.8). The results of this study suggest that the synthesized formulations based on SWNT-CO-Cysteine and PEI 1.8kDa were the most efficient carriers. Considering the decreased cytotoxicity and higher transfection levels, the conjugates bear the potential for effective delivery of genetic materials.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Azadeh Hashem
authors.initials: AH
authors.lastname: Nia
authors.affiliation: Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Eshghi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004220:Disulfides / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000648:ultrastructure; D010957:Plasmids; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004220:Disulfides; D037742:Nanotubes, Carbon; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D004247:DNA
keywords: Bioreducible; Carbon nanotube; Disulfide; Polyethylenimine