title: Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells.
abstract: In this study, single-walled carbon nanotubes (SWCNTs) were covalently attached to poly(ethylene glycol) (PEG) and polyethylenimine (PEI) 10 kDa, or its derivatives, to fabricate efficient carriers for gene delivery. PEI 10 kDa was modified by alkylcarboxylation of its primary amines with a series of ω-bromo-alkylcarboxylic acids to provide a range of vectors with increased lipophilicity. PEI 10 kDa or its alkylcarboxylate derivatives were conjugated to SWCNT-PEG to develop vectors possessing effective DNA condensation ability which can interact with cell membrane via both nano-needle mechanism and electrostatic interactions produced by SWCNT and PEI, respectively. The results demonstrated that SWCNT-PEG-PEI and SWCNT-PEG-derivatives of PEI could condense DNA into particle size less than 150 nm with positive surface charges between 6.3-30.8 mV. To improve the antitumor efficacy, we developed a targeted gene delivery system using a 5 TR1 aptamer. The most efficient vector, which was prepared by attachment of SWCNT-PEG to modified PEI 10 kDa with 10-bromodecanoic acid (10%), showed 8.5-10 folds enhancement in transfection activity at C/P ratio 6 as compared to the gold standard PEI 25 kDa at C/P ratio of 0.8. We also showed that the selected polyplex could efficiently and selectively transfer plasmid shRNA to MUC1 positive cells.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Taghavi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: HashemNia
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.affiliation: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Askarian
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abnouskh@mums.ac.ir.
authors.forename: Khalil
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: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D052156:SELEX Aptamer Technique; D014162:Transfection / Q000379:methods; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C000622068:5TR1 aptamer; D052157:Aptamers, Nucleotide; C494811:BCL2L1 protein, human; C060192:MUC1 protein, human; D018396:Mucin-1; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering; D051020:bcl-X Protein; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: Aptamer; Bcl-xL shRNA; Polyethylenimine; Single-walled carbon nanotubes; Targeted gene delivery