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Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding

Purdie, Laura; Alexander, Cameron; Spain, Sebastian G.; Magnusson, Johannes P.

Authors

Laura Purdie

Sebastian G. Spain

Johannes P. Magnusson



Abstract

DNA-based drug delivery vehicles have displayed promise for the delivery of intercalating drugs. Here, we demonstrate that oligonucleotides modified with an alkyl chain can bind to human serum albumin, mimicking the natural binding of fatty acids. These alkyl-DNA-albumin complexes display excellent serum stability and are capable of strongly binding doxorubicin. Complexes are internalized by cells in vitro, trafficking to the mitochondria, and are capable of delivering doxorubicin with excellent efficiency resulting in cell death. However, the cellular localization of the delivered doxorubicin, and ultimately the complex efficacy, is dependent on the nature of the linker between the alkyl group and the oligonucleotide.

Citation

Purdie, L., Alexander, C., Spain, S. G., & Magnusson, J. P. (2018). Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding. Molecular Pharmaceutics, 15(2), https://doi.org/10.1021/acs.molpharmaceut.7b00805

Journal Article Type Article
Acceptance Date Dec 21, 2017
Online Publication Date Dec 21, 2017
Publication Date Feb 5, 2018
Deposit Date Feb 16, 2018
Publicly Available Date Dec 22, 2018
Journal Molecular Pharmaceutics
Print ISSN 1543-8384
Electronic ISSN 1543-8392
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 15
Issue 2
DOI https://doi.org/10.1021/acs.molpharmaceut.7b00805
Keywords Oligonucleotides, Albumin, Cytotoxic, Prodrug. Mitochondrial targeting
Public URL http://eprints.nottingham.ac.uk/id/eprint/49816
Publisher URL https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.7b00805
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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DNA-FA_Accepted_Manuscript.pdf (1.4 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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