Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LN...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2015-06, Vol.51 (46), p.9499-9502
Main Authors: Edwards, Stacey L, Poongavanam, Vasanthanathan, Kanwar, Jagat R, Roy, Kislay, Hillman, Kristine M, Prasad, Neerati, Leth-Larsen, Rikke, Petersen, Michael, Marušič, Maja, Plavec, Janez, Wengel, Jesper, Veedu, Rakesh N
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - pharmacology
Aptamers, Nucleotide - therapeutic use
Binding
Biomedical materials
Breast
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cancer
Cell Line, Tumor
Cell Movement - drug effects
Cell Proliferation - drug effects
Computer simulation
Effectiveness
Female
Guanine
Human Umbilical Vein Endothelial Cells - drug effects
Humans
Inhibition
Mice, Nude
Molecular Docking Simulation
Molecular dynamics
Molecular Dynamics Simulation
Oligonucleotides - chemistry
Surgical implants
Tumor Burden - drug effects
Vascular Endothelial Growth Factor A - metabolism
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Summary:In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer-VEGF complex blocking its interaction with VEGF-receptor.
ISSN:1359-7345
1364-548X
DOI:10.1039/c5cc02756j