Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding
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...
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| Format: | Article |
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American Chemical Society
2018
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| Online Access: | https://eprints.nottingham.ac.uk/49816/ |
| _version_ | 1848798083874291712 |
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| author | Purdie, Laura Alexander, Cameron Spain, Sebastian G. Magnusson, Johannes P. |
| author_facet | Purdie, Laura Alexander, Cameron Spain, Sebastian G. Magnusson, Johannes P. |
| author_sort | Purdie, Laura |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:14:08Z |
| format | Article |
| id | nottingham-49816 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:14:08Z |
| publishDate | 2018 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-498162020-05-04T19:31:03Z https://eprints.nottingham.ac.uk/49816/ Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding Purdie, Laura Alexander, Cameron Spain, Sebastian G. Magnusson, Johannes P. 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. American Chemical Society 2018-02-05 Article PeerReviewed Purdie, Laura, Alexander, Cameron, 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 Oligonucleotides Albumin Cytotoxic Prodrug. Mitochondrial targeting https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.7b00805 doi:10.1021/acs.molpharmaceut.7b00805 doi:10.1021/acs.molpharmaceut.7b00805 |
| spellingShingle | Oligonucleotides Albumin Cytotoxic Prodrug. Mitochondrial targeting Purdie, Laura Alexander, Cameron Spain, Sebastian G. Magnusson, Johannes P. Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title | Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title_full | Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title_fullStr | Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title_full_unstemmed | Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title_short | Alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| title_sort | alkyl-modified oligonucleotides as intercalating vehicles for doxorubicin uptake via albumin binding |
| topic | Oligonucleotides Albumin Cytotoxic Prodrug. Mitochondrial targeting |
| url | https://eprints.nottingham.ac.uk/49816/ https://eprints.nottingham.ac.uk/49816/ https://eprints.nottingham.ac.uk/49816/ |