Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release

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dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorIjäs, Heinien_US
dc.contributor.authorShen, Boxuanen_US
dc.contributor.authorHeuer-Jungemann, Amelieen_US
dc.contributor.authorKeller, Adrianen_US
dc.contributor.authorKostiainen, Mauri A.en_US
dc.contributor.authorLiedl, Timen_US
dc.contributor.authorIhalainen, Janne A.en_US
dc.contributor.authorLinko, Veikkoen_US
dc.contributor.departmentDepartment of Bioproducts and Biosystemsen
dc.contributor.departmentDepartment of Applied Physicsen
dc.contributor.groupauthorBiohybrid Materialsen
dc.contributor.organizationLudwig Maximilian University of Munichen_US
dc.contributor.organizationPaderborn Universityen_US
dc.contributor.organizationUniversity of Jyväskyläen_US
dc.date.accessioned2021-04-28T06:29:51Z
dc.date.available2021-04-28T06:29:51Z
dc.date.issued2021-04-06en_US
dc.descriptionWe thank Dr H. Häkkänen for technical assistance and S. Julin for the 24HB DNA origami design. We acknowledge the provision of facilities and technical support by Aalto University Bioeconomy Facilities and OtaNano – Nanomicroscopy Center (Aalto-NMC). The research was carried out under the Academy of Finland Centres of Excellence Programme (2014–2019). Academy of Finland [308578 to M.A.K.]; Deutsche Forschungsgemeinschaft [Emmy Noether Programme to A.H.-J., SFB1032 (Project A06) to T.L.]; Emil Aaltonen Foundation [to H.I. and V.L.]; Jane and Aatos Erkko Foundation [to J.A.I. and V.L.]; Sigrid Jusélius Foundation [to V.L.]; Vilho, Yrjö and Kalle Väisälä Foundation of the Finnish Academy of Science and Letters [to V.L.]. Funding for open access charge: Emil Aaltonen Foundation.Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
dc.description.abstractDoxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.en
dc.description.versionPeer revieweden
dc.format.extent15
dc.format.extent3048-3062
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationIjäs, H, Shen, B, Heuer-Jungemann, A, Keller, A, Kostiainen, M A, Liedl, T, Ihalainen, J A & Linko, V 2021, ' Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release ', Nucleic Acids Research, vol. 49, no. 6, pp. 3048-3062 . https://doi.org/10.1093/nar/gkab097en
dc.identifier.doi10.1093/nar/gkab097en_US
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.otherPURE UUID: a2ad801e-19c6-470a-8b0f-d378c1a0a271en_US
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/a2ad801e-19c6-470a-8b0f-d378c1a0a271en_US
dc.identifier.otherPURE LINK: http://www.scopus.com/inward/record.url?scp=85104047846&partnerID=8YFLogxKen_US
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/62144192/CHEM_Ijas_et_al_Unraveling_the_interaction_2021_Nucleic_Acids_Research.pdfen_US
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/107126
dc.identifier.urnURN:NBN:fi:aalto-202104286410
dc.language.isoenen
dc.publisherOXFORD UNIV PRESS
dc.relation.ispartofseriesNucleic Acids Researchen
dc.relation.ispartofseriesVolume 49, issue 6en
dc.rightsopenAccessen
dc.titleUnraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug releaseen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionpublishedVersion
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[article-cris] Kemian tekniikan korkeakoulu / CHEM