From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer

Anne Rodallec,1 Guillaume Sicard,1 Sarah Giacometti,1 Manon Carré,1 Bertrand Pourroy,2 Fanny Bouquet,3 Ariel Savina,3 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino1 1SMARTc Unit, Laboratory of Pharmacokinetics and Toxicology UFR Pharmacy, Center for Research on Cancer of Mar...

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Autores principales:	Rodallec A, Sicard G, Giacometti S, Carré M, Pourroy B, Bouquet F, Savina A, Lacarelle B, Ciccolini J, Fanciullino R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	docetaxel trastuzumab breast cancer immunoliposome spheroids distribution tumor xenograft Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1ff542ded70b40148388d63637375924
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spelling	oai:doaj.org-article:1ff542ded70b40148388d636373759242021-12-02T09:28:43ZFrom 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer1178-2013https://doaj.org/article/1ff542ded70b40148388d636373759242018-10-01T00:00:00Zhttps://www.dovepress.com/from-3d-spheroids-to-tumor-bearing-mice-efficacy-and-distribution-stud-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Anne Rodallec,1 Guillaume Sicard,1 Sarah Giacometti,1 Manon Carré,1 Bertrand Pourroy,2 Fanny Bouquet,3 Ariel Savina,3 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino1 1SMARTc Unit, Laboratory of Pharmacokinetics and Toxicology UFR Pharmacy, Center for Research on Cancer of Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille University, Marseille, France; 2Pharmacy Department, APHM La Conception, Marseille, France; 3Roche Institute, Boulogne Billancourt, France Purpose: Nanoparticles are of rising interest in cancer research, but in vitro canonical cell monolayer models are not suitable to evaluate their efficacy when prototyping candidates. Here, we developed three-dimensional (3D) spheroid models to test the efficacy of trastuzumab-docetaxel immunoliposomes in breast cancer prior to further testing them in vivo. Materials and methods: Immunoliposomes were synthesized using the standard thin film method and maleimide linker. Two human breast cancer cell lines varying in Her2 expression were tested: Her2+ cells derived from metastatic site: mammary breast MDA-MB-453 and triple-negative MDA-MB-231 cells. 3D spheroids were developed and tested with fluorescence detection to evaluate viability. In vivo efficacy and biodistribution studies were performed on xenograft bearing nude mice using fluorescent and bioluminescent imaging. Results: In vitro, antiproliferative efficacy was dependent upon cell type, size of the spheroids, and treatment scheduling, resulting in subsequent changes between tested conditions and in vivo results. Immunoliposomes performed better than free docetaxel + free trastuzumab and ado-trastuzumab emtansine (T-DM1). On MDA-MB-453 and MDA-MB-231 cell growth was reduced by 76% and 25%, when compared to free docetaxel + free trastuzumab and by 85% and 70% when compared to T-DM1, respectively. In vivo studies showed tumor accumulation ranging from 3% up to 15% of the total administered dose in MDA-MB-453 and MDA-MB-231 bearing mice. When compared to free docetaxel + free trastuzumab, tumor growth was reduced by 89% (MDA-MB-453) and 25% (MDA-MB-231) and reduced by 66% (MDA-MB-453) and 29% (MDA-MB-231) when compared to T-DM1, an observation in line with data collected from 3D spheroids experiments. Conclusion: We demonstrated the predictivity of 3D in vitro models when developing and testing nanoparticles in experimental oncology. In vitro and in vivo data showed efficient drug delivery with higher efficacy and prolonged survival with immunoliposomes when compared to current anti-Her2 breast cancer strategies. Keywords: docetaxel, trastuzumab, breast cancer, immunoliposome, spheroids, distribution, tumor xenograftRodallec ASicard GGiacometti SCarré MPourroy BBouquet FSavina ALacarelle BCiccolini JFanciullino RDove Medical Pressarticledocetaxeltrastuzumabbreast cancerimmunoliposomespheroidsdistributiontumor xenograftMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6677-6688 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	docetaxel trastuzumab breast cancer immunoliposome spheroids distribution tumor xenograft Medicine (General) R5-920
spellingShingle	docetaxel trastuzumab breast cancer immunoliposome spheroids distribution tumor xenograft Medicine (General) R5-920 Rodallec A Sicard G Giacometti S Carré M Pourroy B Bouquet F Savina A Lacarelle B Ciccolini J Fanciullino R From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
description	Anne Rodallec,1 Guillaume Sicard,1 Sarah Giacometti,1 Manon Carré,1 Bertrand Pourroy,2 Fanny Bouquet,3 Ariel Savina,3 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino1 1SMARTc Unit, Laboratory of Pharmacokinetics and Toxicology UFR Pharmacy, Center for Research on Cancer of Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille University, Marseille, France; 2Pharmacy Department, APHM La Conception, Marseille, France; 3Roche Institute, Boulogne Billancourt, France Purpose: Nanoparticles are of rising interest in cancer research, but in vitro canonical cell monolayer models are not suitable to evaluate their efficacy when prototyping candidates. Here, we developed three-dimensional (3D) spheroid models to test the efficacy of trastuzumab-docetaxel immunoliposomes in breast cancer prior to further testing them in vivo. Materials and methods: Immunoliposomes were synthesized using the standard thin film method and maleimide linker. Two human breast cancer cell lines varying in Her2 expression were tested: Her2+ cells derived from metastatic site: mammary breast MDA-MB-453 and triple-negative MDA-MB-231 cells. 3D spheroids were developed and tested with fluorescence detection to evaluate viability. In vivo efficacy and biodistribution studies were performed on xenograft bearing nude mice using fluorescent and bioluminescent imaging. Results: In vitro, antiproliferative efficacy was dependent upon cell type, size of the spheroids, and treatment scheduling, resulting in subsequent changes between tested conditions and in vivo results. Immunoliposomes performed better than free docetaxel + free trastuzumab and ado-trastuzumab emtansine (T-DM1). On MDA-MB-453 and MDA-MB-231 cell growth was reduced by 76% and 25%, when compared to free docetaxel + free trastuzumab and by 85% and 70% when compared to T-DM1, respectively. In vivo studies showed tumor accumulation ranging from 3% up to 15% of the total administered dose in MDA-MB-453 and MDA-MB-231 bearing mice. When compared to free docetaxel + free trastuzumab, tumor growth was reduced by 89% (MDA-MB-453) and 25% (MDA-MB-231) and reduced by 66% (MDA-MB-453) and 29% (MDA-MB-231) when compared to T-DM1, an observation in line with data collected from 3D spheroids experiments. Conclusion: We demonstrated the predictivity of 3D in vitro models when developing and testing nanoparticles in experimental oncology. In vitro and in vivo data showed efficient drug delivery with higher efficacy and prolonged survival with immunoliposomes when compared to current anti-Her2 breast cancer strategies. Keywords: docetaxel, trastuzumab, breast cancer, immunoliposome, spheroids, distribution, tumor xenograft
format	article
author	Rodallec A Sicard G Giacometti S Carré M Pourroy B Bouquet F Savina A Lacarelle B Ciccolini J Fanciullino R
author_facet	Rodallec A Sicard G Giacometti S Carré M Pourroy B Bouquet F Savina A Lacarelle B Ciccolini J Fanciullino R
author_sort	Rodallec A
title	From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
title_short	From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
title_full	From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
title_fullStr	From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
title_full_unstemmed	From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
title_sort	from 3d spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/1ff542ded70b40148388d63637375924
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From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer

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