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

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

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: https://nottingham-repository.worktribe.com/output/910160
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.7b00805
• Contract Date: Feb 16, 2018