Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PD...

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Autores principales:	Kimberly A Kelly, Nabeel Bardeesy, Rajesh Anbazhagan, Sushma Gurumurthy, Justin Berger, Herlen Alencar, Ronald A Depinho, Umar Mahmood, Ralph Weissleder
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/4d13fe7230674b9cacf744f778eb9e1b
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spelling	oai:doaj.org-article:4d13fe7230674b9cacf744f778eb9e1b2021-11-25T05:36:59ZTargeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.1549-12771549-167610.1371/journal.pmed.0050085https://doaj.org/article/4d13fe7230674b9cacf744f778eb9e1b2008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18416599/pdf/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents.<h4>Methods and findings</h4>Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides (PTP) were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models.<h4>Conclusions</h4>Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.Kimberly A KellyNabeel BardeesyRajesh AnbazhaganSushma GurumurthyJustin BergerHerlen AlencarRonald A DepinhoUmar MahmoodRalph WeisslederPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 5, Iss 4, p e85 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Kimberly A Kelly Nabeel Bardeesy Rajesh Anbazhagan Sushma Gurumurthy Justin Berger Herlen Alencar Ronald A Depinho Umar Mahmood Ralph Weissleder Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
description	<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents.<h4>Methods and findings</h4>Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides (PTP) were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models.<h4>Conclusions</h4>Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.
format	article
author	Kimberly A Kelly Nabeel Bardeesy Rajesh Anbazhagan Sushma Gurumurthy Justin Berger Herlen Alencar Ronald A Depinho Umar Mahmood Ralph Weissleder
author_facet	Kimberly A Kelly Nabeel Bardeesy Rajesh Anbazhagan Sushma Gurumurthy Justin Berger Herlen Alencar Ronald A Depinho Umar Mahmood Ralph Weissleder
author_sort	Kimberly A Kelly
title	Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
title_short	Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
title_full	Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
title_fullStr	Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
title_full_unstemmed	Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
title_sort	targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/4d13fe7230674b9cacf744f778eb9e1b
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Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.

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