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

Publikation: Bidrag til tidsskriftLetterForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftNucleic Acid Therapeutics
Vol/bind26
Udgave nummer3
Sider (fra-til)183-189
ISSN2159-3337
DOI
StatusUdgivet - 2016

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Citationsformater

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, 26(3), 183-189. https://doi.org/10.1089/nat.2015.0592