Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments

A novel multicellular model composed of epithelial ovarian cancer and fibroblast cells was developed as an in vitro platform to evaluate nanovector delivery and ultimately aid the development of targeted therapies. We hypothesized that the inclusion of peptide-based scaffold (PuraMatrix) in the sphe...

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Autores principales:	Stephen J. Winter, Hunter A. Miller, Jill M. Steinbach-Rankins
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ovarian cancer spheroid model nanoparticle transport Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/aea05537f23f4bd7bb6de5e15a3ccf0d
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spelling	oai:doaj.org-article:aea05537f23f4bd7bb6de5e15a3ccf0d2021-11-25T18:41:33ZMulticellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments10.3390/pharmaceutics131118911999-4923https://doaj.org/article/aea05537f23f4bd7bb6de5e15a3ccf0d2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1891https://doaj.org/toc/1999-4923A novel multicellular model composed of epithelial ovarian cancer and fibroblast cells was developed as an in vitro platform to evaluate nanovector delivery and ultimately aid the development of targeted therapies. We hypothesized that the inclusion of peptide-based scaffold (PuraMatrix) in the spheroid matrix, to represent in vivo tumor microenvironment alterations along with metastatic site conditions, would enhance spheroid cell growth and migration and alter nanovector transport. The model was evaluated by comparing the growth and migration of ovarian cancer cells exposed to stromal cell activation and tissue hypoxia. Fibroblast activation was achieved via the TGF-β1 mediated pathway and tissue hypoxia via 3D spheroids incubated in hypoxia. Surface-modified nanovector transport was assessed via fluorescence and confocal microscopy. Consistent with previous in vivo observations in ascites and at distal metastases, spheroids exposed to activated stromal microenvironment were denser, more contractile and with more migratory cells than nonactivated counterparts. The hypoxic conditions resulted in negative radial spheroid growth over 5 d compared to a radial increase in normoxia. Nanovector penetration attenuated in PuraMatrix regardless of surface modification due to a denser environment. This platform may serve to evaluate nanovector transport based on ovarian ascites and metastatic environments, and longer term, it provide a means to evaluate nanotherapeutic efficacy.Stephen J. WinterHunter A. MillerJill M. Steinbach-RankinsMDPI AGarticleovarian cancerspheroid modelnanoparticle transportPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1891, p 1891 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian cancer spheroid model nanoparticle transport Pharmacy and materia medica RS1-441
spellingShingle	ovarian cancer spheroid model nanoparticle transport Pharmacy and materia medica RS1-441 Stephen J. Winter Hunter A. Miller Jill M. Steinbach-Rankins Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
description	A novel multicellular model composed of epithelial ovarian cancer and fibroblast cells was developed as an in vitro platform to evaluate nanovector delivery and ultimately aid the development of targeted therapies. We hypothesized that the inclusion of peptide-based scaffold (PuraMatrix) in the spheroid matrix, to represent in vivo tumor microenvironment alterations along with metastatic site conditions, would enhance spheroid cell growth and migration and alter nanovector transport. The model was evaluated by comparing the growth and migration of ovarian cancer cells exposed to stromal cell activation and tissue hypoxia. Fibroblast activation was achieved via the TGF-β1 mediated pathway and tissue hypoxia via 3D spheroids incubated in hypoxia. Surface-modified nanovector transport was assessed via fluorescence and confocal microscopy. Consistent with previous in vivo observations in ascites and at distal metastases, spheroids exposed to activated stromal microenvironment were denser, more contractile and with more migratory cells than nonactivated counterparts. The hypoxic conditions resulted in negative radial spheroid growth over 5 d compared to a radial increase in normoxia. Nanovector penetration attenuated in PuraMatrix regardless of surface modification due to a denser environment. This platform may serve to evaluate nanovector transport based on ovarian ascites and metastatic environments, and longer term, it provide a means to evaluate nanotherapeutic efficacy.
format	article
author	Stephen J. Winter Hunter A. Miller Jill M. Steinbach-Rankins
author_facet	Stephen J. Winter Hunter A. Miller Jill M. Steinbach-Rankins
author_sort	Stephen J. Winter
title	Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
title_short	Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
title_full	Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
title_fullStr	Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
title_full_unstemmed	Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments
title_sort	multicellular ovarian cancer model for evaluation of nanovector delivery in ascites and metastatic environments
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/aea05537f23f4bd7bb6de5e15a3ccf0d
work_keys_str_mv	AT stephenjwinter multicellularovariancancermodelforevaluationofnanovectordeliveryinascitesandmetastaticenvironments AT hunteramiller multicellularovariancancermodelforevaluationofnanovectordeliveryinascitesandmetastaticenvironments AT jillmsteinbachrankins multicellularovariancancermodelforevaluationofnanovectordeliveryinascitesandmetastaticenvironments
_version_	1718410795107221504

Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments

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