title: AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.
abstract: AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Malik
authors.affiliation: Departments of Bioengineering, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: O'Toole
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Lavona K
authors.initials: LK
authors.lastname: Casson
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Shelia D
authors.initials: SD
authors.lastname: Thomas
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Gina T
authors.initials: GT
authors.lastname: Bardi
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Elsa Merit
authors.initials: EM
authors.lastname: Reyes-Reyes
authors.affiliation: Departments of Radiology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Chin K
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Departments of Chemical Engineering, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Kyung A
authors.initials: KA
authors.lastname: Kang
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.|Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Bates
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000008:administration & dosage*; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D054118:Nanospheres / Q000008:administration & dosage*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: C513936:AGRO 100; D052157:Aptamers, Nucleotide; D009838:Oligodeoxyribonucleotides; D006046:Gold
keywords: G-quadruplex; nanomedicine; nanoparticles; targeted therapy; triple negative breast cancer