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Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the mali...

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Autores principales: Simón-Gracia, Lorena, Scodeller, Pablo, Fuentes, Sergio Salazar, Vallejo, Vanessa Gómez, Ríos, Xabier, San Sebastián, Eneko, Sidorenko, Valeria, Di Silvio, Desirè, Suck, Meina, De Lorenzi, Federica, Rizzo, Larissa Yokota, von Stillfried, Saskia, Kilk, Kalle, Lammers, Twan, Moya, Sergio E., Teesalu, Tambet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922347/
https://www.ncbi.nlm.nih.gov/pubmed/29721153
http://dx.doi.org/10.18632/oncotarget.24588
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author Simón-Gracia, Lorena
Scodeller, Pablo
Fuentes, Sergio Salazar
Vallejo, Vanessa Gómez
Ríos, Xabier
San Sebastián, Eneko
Sidorenko, Valeria
Di Silvio, Desirè
Suck, Meina
De Lorenzi, Federica
Rizzo, Larissa Yokota
von Stillfried, Saskia
Kilk, Kalle
Lammers, Twan
Moya, Sergio E.
Teesalu, Tambet
author_facet Simón-Gracia, Lorena
Scodeller, Pablo
Fuentes, Sergio Salazar
Vallejo, Vanessa Gómez
Ríos, Xabier
San Sebastián, Eneko
Sidorenko, Valeria
Di Silvio, Desirè
Suck, Meina
De Lorenzi, Federica
Rizzo, Larissa Yokota
von Stillfried, Saskia
Kilk, Kalle
Lammers, Twan
Moya, Sergio E.
Teesalu, Tambet
author_sort Simón-Gracia, Lorena
collection PubMed
description Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions. A tyrosine residue was added to the peptide to allow for (124)I labeling and PET imaging. In a TNBC model in mice, systemic LinTT1-targeted polymersomes accumulated in early tumor lesions more than twice as efficiently as untargeted polymersomes with up to 20% ID/cc at 24 h after administration. The PET-imaging was very sensitive, allowing detection of tumors as small as ∼20 mm(3). Confocal imaging of tumor tissue sections revealed a high degree of vascular exit and stromal penetration of LinTT1-targeted polymersomes and co-localization with tumor-associated macrophages. Our studies show that systemic LinTT1-targeted polymersomes can be potentially used for precision-guided tumor imaging and treatment of TNBC.
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spelling pubmed-59223472018-05-02 Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice Simón-Gracia, Lorena Scodeller, Pablo Fuentes, Sergio Salazar Vallejo, Vanessa Gómez Ríos, Xabier San Sebastián, Eneko Sidorenko, Valeria Di Silvio, Desirè Suck, Meina De Lorenzi, Federica Rizzo, Larissa Yokota von Stillfried, Saskia Kilk, Kalle Lammers, Twan Moya, Sergio E. Teesalu, Tambet Oncotarget Research Paper Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions. A tyrosine residue was added to the peptide to allow for (124)I labeling and PET imaging. In a TNBC model in mice, systemic LinTT1-targeted polymersomes accumulated in early tumor lesions more than twice as efficiently as untargeted polymersomes with up to 20% ID/cc at 24 h after administration. The PET-imaging was very sensitive, allowing detection of tumors as small as ∼20 mm(3). Confocal imaging of tumor tissue sections revealed a high degree of vascular exit and stromal penetration of LinTT1-targeted polymersomes and co-localization with tumor-associated macrophages. Our studies show that systemic LinTT1-targeted polymersomes can be potentially used for precision-guided tumor imaging and treatment of TNBC. Impact Journals LLC 2018-04-10 /pmc/articles/PMC5922347/ /pubmed/29721153 http://dx.doi.org/10.18632/oncotarget.24588 Text en Copyright: © 2018 Simón-Gracia et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Simón-Gracia, Lorena
Scodeller, Pablo
Fuentes, Sergio Salazar
Vallejo, Vanessa Gómez
Ríos, Xabier
San Sebastián, Eneko
Sidorenko, Valeria
Di Silvio, Desirè
Suck, Meina
De Lorenzi, Federica
Rizzo, Larissa Yokota
von Stillfried, Saskia
Kilk, Kalle
Lammers, Twan
Moya, Sergio E.
Teesalu, Tambet
Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title_full Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title_fullStr Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title_full_unstemmed Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title_short Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
title_sort application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922347/
https://www.ncbi.nlm.nih.gov/pubmed/29721153
http://dx.doi.org/10.18632/oncotarget.24588
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