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

Purdie, Laura and Alexander, Cameron and Spain, Sebastian G. and Magnusson, Johannes P. (2018) Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding. Molecular Pharmaceutics, 15 (2). pp. 437-446. ISSN 1543-8392

[img] PDF - Repository staff only until 21 December 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1MB)

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.

Item Type: Article
Keywords: Oligonucleotides, Albumin, Cytotoxic, Prodrug. Mitochondrial targeting
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: https://doi.org/10.1021/acs.molpharmaceut.7b00805
Depositing User: Eprints, Support
Date Deposited: 16 Feb 2018 09:25
Last Modified: 16 Feb 2018 10:46
URI: http://eprints.nottingham.ac.uk/id/eprint/49816

Actions (Archive Staff Only)

Edit View Edit View