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...

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Main Authors: Miller, HL, Antoranz Contera, S, Wollman, AJM, Hirst, A, Dunn, KE, Schröeter, S, O'Connell, D, Leake, MC
Format: Journal article
Language:English
Published: IOP Publishing 2020
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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.
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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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