Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de...

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Autores principales:	Millard M, Yakavets I, Zorin V, Kulmukhamedova A, Marchal S, Bezdetnaya L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Nanodrug tridimensional model distribution accumulation cytotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/479e766c9f9447e4955f2cae1d59eae9
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spelling	oai:doaj.org-article:479e766c9f9447e4955f2cae1d59eae92021-12-02T02:56:02ZDrug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening1178-2013https://doaj.org/article/479e766c9f9447e4955f2cae1d59eae92017-10-01T00:00:00Zhttps://www.dovepress.com/drug-delivery-to-solid-tumors-the--predictive-value-of-the-multicellul-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vand&oelig;uvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs. Keywords: nanodrug, tridimensional model, distribution, accumulation, cytotoxicityMillard MYakavets IZorin VKulmukhamedova AMarchal SBezdetnaya LDove Medical PressarticleNanodrugtridimensional modeldistributionaccumulationcytotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7993-8007 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanodrug tridimensional model distribution accumulation cytotoxicity Medicine (General) R5-920
spellingShingle	Nanodrug tridimensional model distribution accumulation cytotoxicity Medicine (General) R5-920 Millard M Yakavets I Zorin V Kulmukhamedova A Marchal S Bezdetnaya L Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
description	Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vand&oelig;uvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs. Keywords: nanodrug, tridimensional model, distribution, accumulation, cytotoxicity
format	article
author	Millard M Yakavets I Zorin V Kulmukhamedova A Marchal S Bezdetnaya L
author_facet	Millard M Yakavets I Zorin V Kulmukhamedova A Marchal S Bezdetnaya L
author_sort	Millard M
title	Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
title_short	Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
title_full	Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
title_fullStr	Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
title_full_unstemmed	Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
title_sort	drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/479e766c9f9447e4955f2cae1d59eae9
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Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

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