Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

Olof Gissberg, Eman M Zaghloul, Karin E Lundin, Chi-Hung Nguyen, Corinne Landras-Guetta, Jesper Wengel, Rula Zain, C I Edvard Smith

Research output: Contribution to journalLetterResearchpeer-review

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.

Original languageEnglish
JournalNucleic Acid Therapeutics
Volume26
Issue number3
Pages (from-to)183-189
ISSN2159-3337
DOIs
Publication statusPublished - 2016

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Oligonucleotides
Plasticity
Cell Survival
Cells
ellipticine
Nucleic Acids
Poisons
Cytotoxicity
Neoplasms
Derivatives
AGRO 100
Chemical analysis
A549 Cells

Cite this

Gissberg, O., Zaghloul, E. M., Lundin, K. E., Nguyen, C-H., Landras-Guetta, C., Wengel, J., ... Smith, C. I. E. (2016). Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs. Nucleic Acid Therapeutics, 26(3), 183-189. https://doi.org/10.1089/nat.2015.0592
Gissberg, Olof ; Zaghloul, Eman M ; Lundin, Karin E ; Nguyen, Chi-Hung ; Landras-Guetta, Corinne ; Wengel, Jesper ; Zain, Rula ; Smith, C I Edvard. / Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs. In: Nucleic Acid Therapeutics. 2016 ; Vol. 26, No. 3. pp. 183-189.
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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.",
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Gissberg, O, Zaghloul, EM, Lundin, KE, Nguyen, C-H, Landras-Guetta, C, Wengel, J, Zain, R & Smith, CIE 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

Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs. / Gissberg, Olof; Zaghloul, Eman M; Lundin, Karin E; Nguyen, Chi-Hung; Landras-Guetta, Corinne; Wengel, Jesper; Zain, Rula; Smith, C I Edvard.

In: Nucleic Acid Therapeutics, Vol. 26, No. 3, 2016, p. 183-189.

Research output: Contribution to journalLetterResearchpeer-review

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T1 - Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

AU - Gissberg, Olof

AU - Zaghloul, Eman M

AU - Lundin, Karin E

AU - Nguyen, Chi-Hung

AU - Landras-Guetta, Corinne

AU - Wengel, Jesper

AU - Zain, Rula

AU - Smith, C I Edvard

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AB - 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.

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M3 - Letter

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