Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma

Derek Lamont West,1,2 Sarah B White,3 Zhouli Zhang,4 Andrew C Larson,4 Reed A Omary5 1Department of Diagnostic and Interventional Radiology, 2Department of Bioengineering and Nanomedicine, University of Texas Health Sciences Center at Houston, Houston, TX, 3Department of Radiology, Medical College...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	West DL, White SB, Zhang Z, Larson AC, Omary RA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d9e55eea8e7a4a7ab4c5976664512f64
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d9e55eea8e7a4a7ab4c5976664512f64
record_format	dspace
spelling	oai:doaj.org-article:d9e55eea8e7a4a7ab4c5976664512f642021-12-02T01:04:56ZAssessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma1178-2013https://doaj.org/article/d9e55eea8e7a4a7ab4c5976664512f642014-09-01T00:00:00Zhttp://www.dovepress.com/assessment-and-optimization-of-electroporation-assisted-tumoral-nanopa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Derek Lamont West,1,2 Sarah B White,3 Zhouli Zhang,4 Andrew C Larson,4 Reed A Omary5 1Department of Diagnostic and Interventional Radiology, 2Department of Bioengineering and Nanomedicine, University of Texas Health Sciences Center at Houston, Houston, TX, 3Department of Radiology, Medical College of Wisconsin, Milwaukee, WI; 4Department of Radiology, Northwestern University, Chicago, IL; 5Department of Radiology, Vanderbilt University, Nashville, TN, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal form of cancer. In 2012, the incidence of PDAC was 43,920. Five-year survival for patients with PDAC is around 6%, regardless of staging, making PDAC one of the deadliest forms of cancer. One reason for this dismal prognosis is chemoresistance to the current first-line therapy, gemcitabine. There are multiple factors that contribute to the chemoresistance observed in pancreatic cancer. Among them, desmoplasia has been increasingly seen as a significant contributor to chemoresistance. To overcome desmoplastic chemoresistance, several novel methods of treatment have been developed. Electroporation is one such novel treatment. High electrical fields are applied to cells to create pores that increase cell permeability. It has been previously demonstrated that electroporation enhances the therapeutic efficacy of anticancer drugs in pancreatic tumor models. Nanoparticle-based drug delivery systems constitute a second novel method to overcome desmoplastic chemoresistance. Due to their intrinsic design advantages, nanoparticles have been shown to increase the effectiveness of chemotherapeutic agents, while further reducing or even eliminating side effects. To date, there have been no studies evaluating the cumulative effect of combining both nanoparticle and electroporation strategies to overcome chemoresistance in PDAC. Our preliminary studies assessed the in vitro and in vivo uptake of doxorubicin-loaded iron oxide nanoparticles as a function of electroporation voltage and timing of administration in pancreatic adenocarcinoma cells. Our studies demonstrated that addition of electroporation to administration of nanoparticles significantly increased the amount of intracellular iron oxide nanoparticle uptake by a PANC-1 cell line in an athymic nude mouse model of PDAC. Further, electroporation-assisted nanoparticle uptake could be significantly altered by changing the timing of application of electroporation. Keywords: electroporation, nanoparticles, tumoral uptake, pancreatic adenocarcinoma, in vivoWest DLWhite SBZhang ZLarson ACOmary RADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4169-4176 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 West DL White SB Zhang Z Larson AC Omary RA Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
description	Derek Lamont West,1,2 Sarah B White,3 Zhouli Zhang,4 Andrew C Larson,4 Reed A Omary5 1Department of Diagnostic and Interventional Radiology, 2Department of Bioengineering and Nanomedicine, University of Texas Health Sciences Center at Houston, Houston, TX, 3Department of Radiology, Medical College of Wisconsin, Milwaukee, WI; 4Department of Radiology, Northwestern University, Chicago, IL; 5Department of Radiology, Vanderbilt University, Nashville, TN, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal form of cancer. In 2012, the incidence of PDAC was 43,920. Five-year survival for patients with PDAC is around 6%, regardless of staging, making PDAC one of the deadliest forms of cancer. One reason for this dismal prognosis is chemoresistance to the current first-line therapy, gemcitabine. There are multiple factors that contribute to the chemoresistance observed in pancreatic cancer. Among them, desmoplasia has been increasingly seen as a significant contributor to chemoresistance. To overcome desmoplastic chemoresistance, several novel methods of treatment have been developed. Electroporation is one such novel treatment. High electrical fields are applied to cells to create pores that increase cell permeability. It has been previously demonstrated that electroporation enhances the therapeutic efficacy of anticancer drugs in pancreatic tumor models. Nanoparticle-based drug delivery systems constitute a second novel method to overcome desmoplastic chemoresistance. Due to their intrinsic design advantages, nanoparticles have been shown to increase the effectiveness of chemotherapeutic agents, while further reducing or even eliminating side effects. To date, there have been no studies evaluating the cumulative effect of combining both nanoparticle and electroporation strategies to overcome chemoresistance in PDAC. Our preliminary studies assessed the in vitro and in vivo uptake of doxorubicin-loaded iron oxide nanoparticles as a function of electroporation voltage and timing of administration in pancreatic adenocarcinoma cells. Our studies demonstrated that addition of electroporation to administration of nanoparticles significantly increased the amount of intracellular iron oxide nanoparticle uptake by a PANC-1 cell line in an athymic nude mouse model of PDAC. Further, electroporation-assisted nanoparticle uptake could be significantly altered by changing the timing of application of electroporation. Keywords: electroporation, nanoparticles, tumoral uptake, pancreatic adenocarcinoma, in vivo
format	article
author	West DL White SB Zhang Z Larson AC Omary RA
author_facet	West DL White SB Zhang Z Larson AC Omary RA
author_sort	West DL
title	Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title_short	Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title_full	Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title_fullStr	Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title_full_unstemmed	Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title_sort	assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/d9e55eea8e7a4a7ab4c5976664512f64
work_keys_str_mv	AT westdl assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma AT whitesb assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma AT zhangz assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma AT larsonac assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma AT omaryra assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma
_version_	1718403348318650368

Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma

Ejemplares similares