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: Sahar Taghavi, Azadeh HashemNia, Fatemeh Mosaffa, Saeedeh Askarian, Khalil Abnous, Mohammad Ramezani
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 140 Pg. 28-39 (Apr 01 2016) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 26731195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• 5TR1 aptamer
• Aptamers, Nucleotide
• BCL2L1 protein, human
• MUC1 protein, human
• Mucin-1
• Nanotubes, Carbon
• RNA, Small Interfering
• bcl-X Protein
• Polyethylene Glycols
• Polyethyleneimine

Topics

• Aptamers, Nucleotide (chemistry, genetics)
• Blotting, Western
• Cell Line, Tumor
• Cell Survival (genetics)
• Gene Transfer Techniques
• Humans
• MCF-7 Cells
• Microscopy, Atomic Force
• Mucin-1 (genetics, metabolism)
• Nanotubes, Carbon (chemistry)
• Particle Size
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (chemistry)
• RNA, Small Interfering (chemistry, genetics)
• SELEX Aptamer Technique
• Transfection (methods)
• bcl-X Protein (genetics, metabolism)