Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites
Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programma...
Main Authors: | , , , , , , , |
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Format: | Journal article |
Language: | English |
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IOP Publishing
2020
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_version_ | 1797099343588622336 |
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author | Miller, HL Antoranz Contera, S Wollman, AJM Hirst, A Dunn, KE Schröeter, S O'Connell, D Leake, MC |
author_facet | Miller, HL Antoranz Contera, S Wollman, AJM Hirst, A Dunn, KE Schröeter, S O'Connell, D Leake, MC |
author_sort | Miller, HL |
collection | OXFORD |
description | Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery. |
first_indexed | 2024-03-07T05:22:29Z |
format | Journal article |
id | oxford-uuid:df639257-aa7f-42ee-b2f4-c2895369e0f9 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T05:22:29Z |
publishDate | 2020 |
publisher | IOP Publishing |
record_format | dspace |
spelling | oxford-uuid:df639257-aa7f-42ee-b2f4-c2895369e0f92022-03-27T09:39:08ZBiophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sitesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:df639257-aa7f-42ee-b2f4-c2895369e0f9EnglishSymplectic ElementsIOP Publishing2020Miller, HLAntoranz Contera, SWollman, AJMHirst, ADunn, KESchröeter, SO'Connell, DLeake, MCIntercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery. |
spellingShingle | Miller, HL Antoranz Contera, S Wollman, AJM Hirst, A Dunn, KE Schröeter, S O'Connell, D Leake, MC Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title | Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title_full | Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title_fullStr | Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title_full_unstemmed | Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title_short | Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites |
title_sort | biophysical characterization of dna origami nanostructures reveals inaccessibility to intercalation binding sites |
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