title: Single-walled carbon nanotubes functionalized with aptamer and piperazine-polyethylenimine derivative for targeted siRNA delivery into breast cancer cells.
abstract: Epithelial cell adhesion molecule (EpCAM) is a glycosylated type 1 membrane protein which is frequently over expressed in most solid tumors and it has recently been identified as a cancer stem cell (CSC) marker. Specific targeting of CSCs using nano-carriers would enhance treatment efficacy of cancer. In this study, we used a RNA aptamer against EpCAM (EpDT3) attached physically to our newly synthesized non-viral vector, based on single-walled carbon nanotube (SWNT) conjugated to piperazine-polyethylenimine derivative. The DNA transfection efficiency and siRNA delivery activity of the synthesized vector was investigated against upregulated BCL9l, which has been associated with breast and colorectal cancers. The complexes of the vector-aptamer/siRNA could specifically induce apoptosis by more than 20% in MCF-7 cell line as a positive EpCAM than MDA-MB-231 cells which are EpCAM negative. The decrease of BCL9l protein level was observed with western blot analysis in MCF-7 cells indicating the targeted silencing activity of the complex.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, P.O. Box 91775-1365, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, P.O. Box 91775-1365, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Salmasi
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, P.O. Box 91775-1365, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, P.O. Box 91775-1365, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, P.O. Box 91775-1365, 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, P.O. Box 91775-1365, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D050997:Nanomedicine; D037742:Nanotubes, Carbon / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D052157:Aptamers, Nucleotide; C495498:BCL9L protein, human; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D037742:Nanotubes, Carbon; D010879:Piperazines; D034741:RNA, Small Interfering; D014157:Transcription Factors; D011094:Polyethyleneimine
keywords: Aptamer; Epithelial cell adhesion molecule; Gene delivery; Single-walled carbon nanotube; siRNA