Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs
| Autor: | Corinne Landras-Guetta, C. I. Edvard Smith, Eman M. Zaghloul, Jesper Wengel, Karin E. Lundin, Rula Zain, Olof Gissberg, Chi-Hung Nguyen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Survival Aptamer media_common.quotation_subject Oligonucleotides Biochemistry 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Neoplasms Drug Discovery Genetics Humans Viability assay Cytotoxicity Internalization Molecular Biology media_common Oligonucleotide Chemistry Circular Dichroism Aptamers Nucleotide Molecular biology G-Quadruplexes 030104 developmental biology Oligodeoxyribonucleotides A549 Cells 030220 oncology & carcinogenesis Cancer cell Nucleic acid Biophysics Molecular Medicine Nucleolin |
| Zdroj: | Gissberg, O, Zaghloul, E M, Lundin, K E, Nguyen, C-H, Landras-Guetta, C, Wengel, J, Zain, R & Smith, C I E 2016, ' Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs ', Nucleic Acid Therapeutics, vol. 26, no. 3, pp. 183-189 . https://doi.org/10.1089/nat.2015.0592 |
| ISSN: | 2159-3345 2159-3337 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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