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Targeting the tumor vasculature with engineered cystine-knot miniproteins
The extra domain B splice variant (EDB) of human fibronectin selectively expressed in the tumor vasculature is an attractive target for cancer imaging and therapy. Here, we describe the generation and characterization of EDB-specific optical imaging probes. By screening combinatorial cystine-knot mi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962393/ https://www.ncbi.nlm.nih.gov/pubmed/31941901 http://dx.doi.org/10.1038/s41467-019-13948-y |
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author | Lui, Bonny Gaby Salomon, Nadja Wüstehube-Lausch, Joycelyn Daneschdar, Matin Schmoldt, Hans-Ulrich Türeci, Özlem Sahin, Ugur |
author_facet | Lui, Bonny Gaby Salomon, Nadja Wüstehube-Lausch, Joycelyn Daneschdar, Matin Schmoldt, Hans-Ulrich Türeci, Özlem Sahin, Ugur |
author_sort | Lui, Bonny Gaby |
collection | PubMed |
description | The extra domain B splice variant (EDB) of human fibronectin selectively expressed in the tumor vasculature is an attractive target for cancer imaging and therapy. Here, we describe the generation and characterization of EDB-specific optical imaging probes. By screening combinatorial cystine-knot miniprotein libraries with phage display technology we discover exquisitely EDB-specific ligands that share a distinctive motif. Probes with a binding constant in the picomolar range are generated by chemical oligomerization of selected ligands and fluorophore conjugation. We show by fluorescence imaging that the probes stain EDB in tissue sections derived from human U-87 MG glioblastoma xenografts in mice. Moreover, we demonstrate selective accumulation and retention of intravenously administered probes in the tumor tissue of mice with U-87 MG glioblastoma xenografts by in vivo and ex vivo fluorescence imaging. These data warrants further pursuit of the selected cystine-knot miniproteins for in vivo imaging applications. |
format | Online Article Text |
id | pubmed-6962393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69623932020-01-17 Targeting the tumor vasculature with engineered cystine-knot miniproteins Lui, Bonny Gaby Salomon, Nadja Wüstehube-Lausch, Joycelyn Daneschdar, Matin Schmoldt, Hans-Ulrich Türeci, Özlem Sahin, Ugur Nat Commun Article The extra domain B splice variant (EDB) of human fibronectin selectively expressed in the tumor vasculature is an attractive target for cancer imaging and therapy. Here, we describe the generation and characterization of EDB-specific optical imaging probes. By screening combinatorial cystine-knot miniprotein libraries with phage display technology we discover exquisitely EDB-specific ligands that share a distinctive motif. Probes with a binding constant in the picomolar range are generated by chemical oligomerization of selected ligands and fluorophore conjugation. We show by fluorescence imaging that the probes stain EDB in tissue sections derived from human U-87 MG glioblastoma xenografts in mice. Moreover, we demonstrate selective accumulation and retention of intravenously administered probes in the tumor tissue of mice with U-87 MG glioblastoma xenografts by in vivo and ex vivo fluorescence imaging. These data warrants further pursuit of the selected cystine-knot miniproteins for in vivo imaging applications. Nature Publishing Group UK 2020-01-15 /pmc/articles/PMC6962393/ /pubmed/31941901 http://dx.doi.org/10.1038/s41467-019-13948-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lui, Bonny Gaby Salomon, Nadja Wüstehube-Lausch, Joycelyn Daneschdar, Matin Schmoldt, Hans-Ulrich Türeci, Özlem Sahin, Ugur Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title | Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title_full | Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title_fullStr | Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title_full_unstemmed | Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title_short | Targeting the tumor vasculature with engineered cystine-knot miniproteins |
title_sort | targeting the tumor vasculature with engineered cystine-knot miniproteins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962393/ https://www.ncbi.nlm.nih.gov/pubmed/31941901 http://dx.doi.org/10.1038/s41467-019-13948-y |
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