Cargando…

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

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 chemore...

Descripción completa

Detalles Bibliográficos
Autores principales: West, Derek Lamont, White, Sarah B, Zhang, Zhouli, Larson, Andrew C, Omary, Reed A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159314/
https://www.ncbi.nlm.nih.gov/pubmed/25214781
http://dx.doi.org/10.2147/IJN.S63324
_version_ 1782334200800608256
author West, Derek Lamont
White, Sarah B
Zhang, Zhouli
Larson, Andrew C
Omary, Reed A
author_facet West, Derek Lamont
White, Sarah B
Zhang, Zhouli
Larson, Andrew C
Omary, Reed A
author_sort West, Derek Lamont
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4159314
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-41593142014-09-11 Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma West, Derek Lamont White, Sarah B Zhang, Zhouli Larson, Andrew C Omary, Reed A Int J Nanomedicine Original Research 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. Dove Medical Press 2014-09-01 /pmc/articles/PMC4159314/ /pubmed/25214781 http://dx.doi.org/10.2147/IJN.S63324 Text en © 2014 West et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
West, Derek Lamont
White, Sarah B
Zhang, Zhouli
Larson, Andrew C
Omary, Reed A
Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159314/
https://www.ncbi.nlm.nih.gov/pubmed/25214781
http://dx.doi.org/10.2147/IJN.S63324
work_keys_str_mv AT westdereklamont assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma
AT whitesarahb assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma
AT zhangzhouli assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma
AT larsonandrewc assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma
AT omaryreeda assessmentandoptimizationofelectroporationassistedtumoralnanoparticleuptakeinanudemousemodelofpancreaticductaladenocarcinoma