title: Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types.
abstract: We report the design of a nanoconstruct that can function as a cell-type independent agent by targeting the ubiquitous protein nucleolin. Gold nanostars (AuNS) loaded with high densities of nucleolin-specific DNA aptamer AS1411 (Apt-AuNS) produced anticancer effects in a panel of 12 cancer lines containing four representative subcategories. We found that the nanoconstructs could be internalized by cancer cells and trafficked to perinuclear regions. Apt-AuNS resulted in downregulation of antiapoptotic Bcl-2 mRNA expression by ca. 200% compared to cells without the nanoconstructs. The caspase 3/7 activity (apoptosis) and cell death in cancer cells treated with Apt-AuNS increased by 1.5 times and by ca. 17%, respectively, compared to cells treated with free AS1411 at over 10 times the concentration. Moreover, light-triggered release of aptamer from the AuNS further enhanced the in vitro efficacy of the nanoconstructs in the cancer line panel with a 2-fold increase in caspase activity and a 40% decrease in cell viability compared to treatment with Apt-AuNS only. In contrast, treatments of the nanoconstructs with or without light-triggered release on a panel of normal cell lines had no adverse effects.
authors.affiliation: Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Duncan Hieu M
authors.initials: DH
authors.lastname: Dam
authors.forename: Kayla S B
authors.initials: KS
authors.lastname: Culver
authors.forename: Teri W
authors.initials: TW
authors.lastname: Odom
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016503:Drug Delivery Systems; D019254:Genes, bcl-2 / Q000235:genetics; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D006046:Gold; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100