<div class="csl-bib-body">
<div class="csl-entry">Steen, E. J. L., Jørgensen, J. T., Johann, K., Nørregaard, K., Sohr, B., Svatunek, D., Birke, A., Shalgunov, V., Edem, P. E., Rossin, R., Seidl, C., Schmid, F., Robillard, M. S., Kristensen, J. L., Mikula, H., Barz, M., Kjær, A., & Herth, M. M. (2019). Trans-Cyclooctene-Functionalized PeptoBrushes with Improved Reaction Kinetics of the Tetrazine Ligation for Pretargeted Nuclear Imaging. <i>ACS Nano</i>, <i>14</i>(1), 568–584. https://doi.org/10.1021/acsnano.9b06905</div>
</div>
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dc.identifier.issn
1936-0851
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/140107
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dc.description.abstract
Tumor targeting using agents with slow pharmacokinetics represents a major challenge in nuclear imaging and targeted radionuclide therapy as they most often result in low imaging contrast and high radiation dose to healthy tissue. To address this challenge, we developed a polymer-based targeting agent that can be used for pretargeted imaging and thus separates tumor accumulation from the imaging step in time. The developed targeting agent is based on polypeptide-graft-polypeptoid polymers (PeptoBrushes) functionalized with trans-cyclooctene (TCO). The complementary 111In-labeled imaging agent is a 1,2,4,5-tetrazine derivative, which can react with aforementioned TCO-modified PeptoBrushes in a rapid bioorthogonal ligation. A high degree of TCO loading (up to 30%) was achieved, without altering the physicochemical properties of the polymeric nanoparticle. The highest degree of TCO loading resulted in significantly increased reaction rates (77-fold enhancement) compared to those with small molecule TCO moieties when using lipophilic tetrazines. Based on computer simulations, we hypothesize that this increase is a result of hydrophobic effects and significant rearrangements within the polymer framework, in which hydrophobic patches of TCO moieties are formed. These patches attract lipophilic tetrazines, leading to increased reaction rates in the bioorthogonal ligation. The most reactive system was evaluated as a targeting agent for pretargeted imaging in tumor-bearing mice. After the setup was optimized, sufficient tumor-to-background ratios were achieved as early as 2 h after administration of the tetrazine imaging agent, which further improved at 22 h, enabling clear visualization of CT-26 tumors. These findings show the potential of PeptoBrushes to be used as a pretargeting agent when an optimized dose of polymer is used.
en
dc.language.iso
en
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dc.relation.ispartof
ACS Nano
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dc.subject
General Engineering
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dc.subject
General Materials Science
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dc.subject
General Physics and Astronomy
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dc.title
Trans-Cyclooctene-Functionalized PeptoBrushes with Improved Reaction Kinetics of the Tetrazine Ligation for Pretargeted Nuclear Imaging
en
dc.type
Artikel
de
dc.type
Article
en
dc.description.startpage
568
-
dc.description.endpage
584
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dc.type.category
Original Research Article
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tuw.container.volume
14
-
tuw.container.issue
1
-
tuw.journal.peerreviewed
true
-
tuw.peerreviewed
true
-
wb.publication.intCoWork
International Co-publication
-
tuw.researchTopic.id
X1
-
tuw.researchTopic.name
außerhalb der gesamtuniversitären Forschungsschwerpunkte
-
tuw.researchTopic.value
100
-
dcterms.isPartOf.title
ACS Nano
-
tuw.publication.orgunit
E163-03-2 - Forschungsgruppe Molekulare Chemie und Chemische Biologie
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tuw.publisher.doi
10.1021/acsnano.9b06905
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dc.identifier.eissn
1936-086X
-
dc.description.numberOfPages
17
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tuw.author.orcid
0000-0002-3690-2087
-
tuw.author.orcid
0000-0002-5613-1267
-
tuw.author.orcid
0000-0002-9218-9722
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tuw.author.orcid
0000-0002-1749-9034
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tuw.author.orcid
0000-0002-7788-513X
-
wb.sci
true
-
wb.sciencebranch
Chemie
-
wb.sciencebranch
Biologie
-
wb.sciencebranch.oefos
1040
-
wb.sciencebranch.oefos
1060
-
wb.facultyfocus
Außerhalb der primären Forschungsgebiete der Fakultät
de
wb.facultyfocus
Outside the Faculty's primary research activities
en
item.openairecristype
http://purl.org/coar/resource_type/c_18cf
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item.openairecristype
http://purl.org/coar/resource_type/c_18cf
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none
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item.fulltext
no Fulltext
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item.openairetype
Artikel
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item.openairetype
Article
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Publications
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Publications
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item.languageiso639-1
en
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crisitem.author.dept
E163-03-2 - Forschungsgruppe Molekulare Chemie und Chemische Biologie
-
crisitem.author.dept
E163-03-2 - Forschungsgruppe Molekulare Chemie und Chemische Biologie
-
crisitem.author.dept
E163-03-2 - Forschungsgruppe Molekulare Chemie und Chemische Biologie
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crisitem.author.orcid
0000-0003-1101-2376
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crisitem.author.orcid
0000-0002-9218-9722
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crisitem.author.parentorg
E163-03 - Forschungsbereich Organische und Biologische Chemie
-
crisitem.author.parentorg
E163-03 - Forschungsbereich Organische und Biologische Chemie
-
crisitem.author.parentorg
E163-03 - Forschungsbereich Organische und Biologische Chemie