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uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection
Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy dur...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881230/ https://www.ncbi.nlm.nih.gov/pubmed/24396518 http://dx.doi.org/10.7150/thno.7409 |
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author | Yang, Lily Sajja, Hari Krishna Cao, Zehong Qian, Weiping Bender, Laura Marcus, Adam I. Lipowska, Malgorzata Wood, William C. Wang, Y. Andrew |
author_facet | Yang, Lily Sajja, Hari Krishna Cao, Zehong Qian, Weiping Bender, Laura Marcus, Adam I. Lipowska, Malgorzata Wood, William C. Wang, Y. Andrew |
author_sort | Yang, Lily |
collection | PubMed |
description | Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. |
format | Online Article Text |
id | pubmed-3881230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-38812302014-01-06 uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection Yang, Lily Sajja, Hari Krishna Cao, Zehong Qian, Weiping Bender, Laura Marcus, Adam I. Lipowska, Malgorzata Wood, William C. Wang, Y. Andrew Theranostics Research Paper Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. Ivyspring International Publisher 2013-12-17 /pmc/articles/PMC3881230/ /pubmed/24396518 http://dx.doi.org/10.7150/thno.7409 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Yang, Lily Sajja, Hari Krishna Cao, Zehong Qian, Weiping Bender, Laura Marcus, Adam I. Lipowska, Malgorzata Wood, William C. Wang, Y. Andrew uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title | uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title_full | uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title_fullStr | uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title_full_unstemmed | uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title_short | uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection |
title_sort | upar-targeted optical imaging contrasts as theranostic agents for tumor margin detection |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881230/ https://www.ncbi.nlm.nih.gov/pubmed/24396518 http://dx.doi.org/10.7150/thno.7409 |
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