Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells

Schematic illustration of targeted shRNA delivery using aptamer-conjugated polyplexes. [Display omitted] •Eight types of nanoparticles were synthesized by covalent attachment of SWCNT to PEG and PEI 10kDa or its derivatives•Fabricated nanoparticles showed better transfection efficiency and less cyto...

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Veröffentlicht in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2016-04, Vol.140, p.28-39
Hauptverfasser: Taghavi, Sahar, HashemNia, Azadeh, Mosaffa, Fatemeh, Askarian, Saeedeh, Abnous, Khalil, Ramezani, Mohammad
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container_title Colloids and surfaces, B, Biointerfaces
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creator Taghavi, Sahar
HashemNia, Azadeh
Mosaffa, Fatemeh
Askarian, Saeedeh
Abnous, Khalil
Ramezani, Mohammad
description Schematic illustration of targeted shRNA delivery using aptamer-conjugated polyplexes. [Display omitted] •Eight types of nanoparticles were synthesized by covalent attachment of SWCNT to PEG and PEI 10kDa or its derivatives•Fabricated nanoparticles showed better transfection efficiency and less cytotoxicity as compared with unmodified PEI 10kDa.•5TR1 Apt-conjugated nanoparticles efficiently delivered plasmid Bcl-xL shRNA to breast cancer cell line (MCF7).•Our results demonstrated the potential and specificity of functionalized Apt-carbon nanotubes conjugates for increasing the induction of apoptosis in tumor cells by suppression of Bcl-xL transcript. In this study, single-walled carbon nanotubes (SWCNTs) were covalently attached to poly(ethylene glycol) (PEG) and polyethylenimine (PEI) 10kDa, or its derivatives, to fabricate efficient carriers for gene delivery. PEI 10kDa 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 10kDa 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 150nm with positive surface charges between 6.3–30.8mV. To improve the antitumor efficacy, we developed a targeted gene delivery system using a 5TR1 aptamer. The most efficient vector, which was prepared by attachment of SWCNT-PEG to modified PEI 10kDa 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 25kDa 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.
doi_str_mv 10.1016/j.colsurfb.2015.12.021
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[Display omitted] •Eight types of nanoparticles were synthesized by covalent attachment of SWCNT to PEG and PEI 10kDa or its derivatives•Fabricated nanoparticles showed better transfection efficiency and less cytotoxicity as compared with unmodified PEI 10kDa.•5TR1 Apt-conjugated nanoparticles efficiently delivered plasmid Bcl-xL shRNA to breast cancer cell line (MCF7).•Our results demonstrated the potential and specificity of functionalized Apt-carbon nanotubes conjugates for increasing the induction of apoptosis in tumor cells by suppression of Bcl-xL transcript. In this study, single-walled carbon nanotubes (SWCNTs) were covalently attached to poly(ethylene glycol) (PEG) and polyethylenimine (PEI) 10kDa, or its derivatives, to fabricate efficient carriers for gene delivery. PEI 10kDa 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 10kDa 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 150nm with positive surface charges between 6.3–30.8mV. To improve the antitumor efficacy, we developed a targeted gene delivery system using a 5TR1 aptamer. The most efficient vector, which was prepared by attachment of SWCNT-PEG to modified PEI 10kDa 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 25kDa 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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26731195</pmid><doi>10.1016/j.colsurfb.2015.12.021</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-6314-0164</orcidid></addata></record>
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subjects Aptamer
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - genetics
bcl-X Protein - genetics
bcl-X Protein - metabolism
Bcl-xL shRNA
Blotting, Western
Cell Line, Tumor
Cell Survival - genetics
Condensing
Deoxyribonucleic acid
Derivatives
Gene Transfer Techniques
Genes
Humans
Mathematical analysis
MCF-7 Cells
Microscopy, Atomic Force
Mucin-1 - genetics
Mucin-1 - metabolism
Nanotubes, Carbon - chemistry
Particle Size
Polyetherimides
Polyethylene Glycols - chemistry
Polyethyleneimine - chemistry
Polyethylenimine
RNA, Small Interfering - chemistry
RNA, Small Interfering - genetics
SELEX Aptamer Technique
Single wall carbon nanotubes
Single-walled carbon nanotubes
Targeted gene delivery
Transfection - methods
Vectors (mathematics)
title Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells
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