title: Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs.
abstract: AS1411 is a g-quadruplex-forming aptamer capable of selectively entering cancer cells by nucleolin receptor-mediated uptake. In this study, we investigated the cell internalization properties and plasticity of AS1411 carrying different locked nucleic acid-containing cargo oligonucleotides (ONs) for delivery into A549 and U2OS cells. We found that internalization efficiency is highly governed by ON cargo chemistry and composition since the inherent antitumor properties of AS1411 were lost when attached to a nontoxic ON, noTox. However, a toxic ON, Tox, demonstrated potent cytotoxicity after aptamer-mediated uptake in A549 cells. We also examined the effect of unlocked nucleic acid (UNA) modifications in the loop region of the aptamer, and how the cargo ONs and UNA incorporation affect the secondary structure of AS1411, in the presence or absence of two novel ellipticine derivatives. These findings add new insights to the design and future applications of aptamer-guided delivery of ON cargo to cancer cells.
authors: 1 Department of Laboratory Medicine, Karolinska Institutet, and Karolinska University Hospital , Huddinge, Sweden .
authors: Olof
authors: O
authors: Gissberg
authors: 1 Department of Laboratory Medicine, Karolinska Institutet, and Karolinska University Hospital , Huddinge, Sweden .
authors: Eman M
authors: EM
authors: Zaghloul
authors: 1 Department of Laboratory Medicine, Karolinska Institutet, and Karolinska University Hospital , Huddinge, Sweden .
authors: Karin E
authors: KE
authors: Lundin
authors: 2 Institut Curie, PSL Research University , UMR 9187-U 1196, CNRS-Institut Curie, INSERM, Centre Universitaire, Orsay, France .
authors: Chi-Hung
authors: CH
authors: Nguyen
authors: 2 Institut Curie, PSL Research University , UMR 9187-U 1196, CNRS-Institut Curie, INSERM, Centre Universitaire, Orsay, France .
authors: Corinne
authors: C
authors: Landras-Guetta
authors: 3 Department of Physics, Chemistry and Pharmacy, Nucleic Acid Centre, University of Southern Denmark , Odense, Denmark .
authors: Jesper
authors: J
authors: Wengel
authors: 1 Department of Laboratory Medicine, Karolinska Institutet, and Karolinska University Hospital , Huddinge, Sweden .|4 Department of Clinical Genetics, Centre for Rare Diseases, Karolinska University Hospital , Stockholm, Sweden .
authors: Rula
authors: R
authors: Zain
authors: 1 Department of Laboratory Medicine, Karolinska Institutet, and Karolinska University Hospital , Huddinge, Sweden .
authors: C I Edvard
authors: CI
authors: Smith
mesh_terms: D000072283:A549 Cells; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D054856:G-Quadruplexes; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000235:genetics; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: C513936:AGRO 100; D052157:Aptamers, Nucleotide; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; C477371:locked nucleic acid