Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications

The development of DNA nanotechnology has enabled the creation of diverse nanomaterials with significant potential in biological applications, such as sensing or drug delivery. From DNA origami to wireframe nanostructures, several strategies have been developed to deliver nucleic acid therapeutics i...

Full description

Saved in:
Bibliographic Details
Published in:Small science 2024-12
Main Authors: Faiad, Sinan, Laurent, Quentin, Asohan, Jathavan, Brown, Tyler, Prinzen, Alexander, Sleiman, Hanadi Farouk
Format: Article
Language:English
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites cdi_FETCH-LOGICAL-c164t-433b02193b705e3357d463cc010eaa3006653885052b535d04735c353546dda63
container_end_page
container_issue
container_start_page
container_title Small science
container_volume
creator Faiad, Sinan
Laurent, Quentin
Asohan, Jathavan
Brown, Tyler
Prinzen, Alexander
Sleiman, Hanadi Farouk
description The development of DNA nanotechnology has enabled the creation of diverse nanomaterials with significant potential in biological applications, such as sensing or drug delivery. From DNA origami to wireframe nanostructures, several strategies have been developed to deliver nucleic acid therapeutics into cells. However, these self‐assembled structures suffer from poor stability in biological media due to low concentrations of divalent cations, degradation by nucleases, and thermal denaturation. Herein, a site‐specific crosslinking method based on thiol‐disulfide exchange to stabilize a wireframe DNA nanocube is developed. With nearly quantitative crosslinking yields, the structure retains its structural integrity in conditions that mimic physiological environments. This results in improved cellular uptake, likely due to more favorable interaction with cell‐surface scavenger receptors, followed by endocytosis. This study paves the way for in vivo applications of DNA wireframe nanostructures by removing one of the major bottlenecks for their translation from in vitro to preclinical work.
doi_str_mv 10.1002/smsc.202400471
format article
fullrecord <record><control><sourceid>crossref</sourceid><recordid>TN_cdi_crossref_primary_10_1002_smsc_202400471</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>10_1002_smsc_202400471</sourcerecordid><originalsourceid>FETCH-LOGICAL-c164t-433b02193b705e3357d463cc010eaa3006653885052b535d04735c353546dda63</originalsourceid><addsrcrecordid>eNpNkE1OwzAQRi0EElXplrUvkDL22E66LG35kUpZFNaRYzvBkMZRnC7YcQTOyElIBEKs5mn0zWjmEXLJYM4A-FU8RDPnwAWASNkJmXCVZYkAoU7_8TmZxfgKw4BkLF3wCan2vndfH5_71hlfekPXPh7r0tux-eCs172zdNWFGGvfvPmmoqGk692S7nQTzLFwkZaho5vmRTdmiF77UIfKG13TZdvWA_Q-NPGCnJW6jm72W6fk-WbztLpLto-396vlNjFMiT4RiAVwtsAiBekQZWqFQmOAgdMaAZSSmGUSJC8kSjs8i9LggEJZqxVOyfxnrxlP7lyZt50_6O49Z5CPpvLRVP5nCr8BfeldfQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications</title><source>Open Access: Wiley-Blackwell Open Access Journals</source><source>Publicly Available Content Database</source><creator>Faiad, Sinan ; Laurent, Quentin ; Asohan, Jathavan ; Brown, Tyler ; Prinzen, Alexander ; Sleiman, Hanadi Farouk</creator><creatorcontrib>Faiad, Sinan ; Laurent, Quentin ; Asohan, Jathavan ; Brown, Tyler ; Prinzen, Alexander ; Sleiman, Hanadi Farouk</creatorcontrib><description>The development of DNA nanotechnology has enabled the creation of diverse nanomaterials with significant potential in biological applications, such as sensing or drug delivery. From DNA origami to wireframe nanostructures, several strategies have been developed to deliver nucleic acid therapeutics into cells. However, these self‐assembled structures suffer from poor stability in biological media due to low concentrations of divalent cations, degradation by nucleases, and thermal denaturation. Herein, a site‐specific crosslinking method based on thiol‐disulfide exchange to stabilize a wireframe DNA nanocube is developed. With nearly quantitative crosslinking yields, the structure retains its structural integrity in conditions that mimic physiological environments. This results in improved cellular uptake, likely due to more favorable interaction with cell‐surface scavenger receptors, followed by endocytosis. This study paves the way for in vivo applications of DNA wireframe nanostructures by removing one of the major bottlenecks for their translation from in vitro to preclinical work.</description><identifier>ISSN: 2688-4046</identifier><identifier>EISSN: 2688-4046</identifier><identifier>DOI: 10.1002/smsc.202400471</identifier><language>eng</language><ispartof>Small science, 2024-12</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c164t-433b02193b705e3357d463cc010eaa3006653885052b535d04735c353546dda63</cites><orcidid>0000-0003-1023-1198 ; 0000-0002-5100-0532</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids></links><search><creatorcontrib>Faiad, Sinan</creatorcontrib><creatorcontrib>Laurent, Quentin</creatorcontrib><creatorcontrib>Asohan, Jathavan</creatorcontrib><creatorcontrib>Brown, Tyler</creatorcontrib><creatorcontrib>Prinzen, Alexander</creatorcontrib><creatorcontrib>Sleiman, Hanadi Farouk</creatorcontrib><title>Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications</title><title>Small science</title><description>The development of DNA nanotechnology has enabled the creation of diverse nanomaterials with significant potential in biological applications, such as sensing or drug delivery. From DNA origami to wireframe nanostructures, several strategies have been developed to deliver nucleic acid therapeutics into cells. However, these self‐assembled structures suffer from poor stability in biological media due to low concentrations of divalent cations, degradation by nucleases, and thermal denaturation. Herein, a site‐specific crosslinking method based on thiol‐disulfide exchange to stabilize a wireframe DNA nanocube is developed. With nearly quantitative crosslinking yields, the structure retains its structural integrity in conditions that mimic physiological environments. This results in improved cellular uptake, likely due to more favorable interaction with cell‐surface scavenger receptors, followed by endocytosis. This study paves the way for in vivo applications of DNA wireframe nanostructures by removing one of the major bottlenecks for their translation from in vitro to preclinical work.</description><issn>2688-4046</issn><issn>2688-4046</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpNkE1OwzAQRi0EElXplrUvkDL22E66LG35kUpZFNaRYzvBkMZRnC7YcQTOyElIBEKs5mn0zWjmEXLJYM4A-FU8RDPnwAWASNkJmXCVZYkAoU7_8TmZxfgKw4BkLF3wCan2vndfH5_71hlfekPXPh7r0tux-eCs172zdNWFGGvfvPmmoqGk692S7nQTzLFwkZaho5vmRTdmiF77UIfKG13TZdvWA_Q-NPGCnJW6jm72W6fk-WbztLpLto-396vlNjFMiT4RiAVwtsAiBekQZWqFQmOAgdMaAZSSmGUSJC8kSjs8i9LggEJZqxVOyfxnrxlP7lyZt50_6O49Z5CPpvLRVP5nCr8BfeldfQ</recordid><startdate>20241212</startdate><enddate>20241212</enddate><creator>Faiad, Sinan</creator><creator>Laurent, Quentin</creator><creator>Asohan, Jathavan</creator><creator>Brown, Tyler</creator><creator>Prinzen, Alexander</creator><creator>Sleiman, Hanadi Farouk</creator><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-1023-1198</orcidid><orcidid>https://orcid.org/0000-0002-5100-0532</orcidid></search><sort><creationdate>20241212</creationdate><title>Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications</title><author>Faiad, Sinan ; Laurent, Quentin ; Asohan, Jathavan ; Brown, Tyler ; Prinzen, Alexander ; Sleiman, Hanadi Farouk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c164t-433b02193b705e3357d463cc010eaa3006653885052b535d04735c353546dda63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Faiad, Sinan</creatorcontrib><creatorcontrib>Laurent, Quentin</creatorcontrib><creatorcontrib>Asohan, Jathavan</creatorcontrib><creatorcontrib>Brown, Tyler</creatorcontrib><creatorcontrib>Prinzen, Alexander</creatorcontrib><creatorcontrib>Sleiman, Hanadi Farouk</creatorcontrib><collection>CrossRef</collection><jtitle>Small science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Faiad, Sinan</au><au>Laurent, Quentin</au><au>Asohan, Jathavan</au><au>Brown, Tyler</au><au>Prinzen, Alexander</au><au>Sleiman, Hanadi Farouk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications</atitle><jtitle>Small science</jtitle><date>2024-12-12</date><risdate>2024</risdate><issn>2688-4046</issn><eissn>2688-4046</eissn><abstract>The development of DNA nanotechnology has enabled the creation of diverse nanomaterials with significant potential in biological applications, such as sensing or drug delivery. From DNA origami to wireframe nanostructures, several strategies have been developed to deliver nucleic acid therapeutics into cells. However, these self‐assembled structures suffer from poor stability in biological media due to low concentrations of divalent cations, degradation by nucleases, and thermal denaturation. Herein, a site‐specific crosslinking method based on thiol‐disulfide exchange to stabilize a wireframe DNA nanocube is developed. With nearly quantitative crosslinking yields, the structure retains its structural integrity in conditions that mimic physiological environments. This results in improved cellular uptake, likely due to more favorable interaction with cell‐surface scavenger receptors, followed by endocytosis. This study paves the way for in vivo applications of DNA wireframe nanostructures by removing one of the major bottlenecks for their translation from in vitro to preclinical work.</abstract><doi>10.1002/smsc.202400471</doi><orcidid>https://orcid.org/0000-0003-1023-1198</orcidid><orcidid>https://orcid.org/0000-0002-5100-0532</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2688-4046
ispartof Small science, 2024-12
issn 2688-4046
2688-4046
language eng
recordid cdi_crossref_primary_10_1002_smsc_202400471
source Open Access: Wiley-Blackwell Open Access Journals; Publicly Available Content Database
title Site‐Specific Disulfide‐Mediated Crosslinking of DNA Nanocubes for Enhanced Biological Applications
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T12%3A47%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-crossref&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Site%E2%80%90Specific%20Disulfide%E2%80%90Mediated%20Crosslinking%20of%20DNA%20Nanocubes%20for%20Enhanced%20Biological%20Applications&rft.jtitle=Small%20science&rft.au=Faiad,%20Sinan&rft.date=2024-12-12&rft.issn=2688-4046&rft.eissn=2688-4046&rft_id=info:doi/10.1002/smsc.202400471&rft_dat=%3Ccrossref%3E10_1002_smsc_202400471%3C/crossref%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c164t-433b02193b705e3357d463cc010eaa3006653885052b535d04735c353546dda63%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true