Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer

Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer

Anne Rodallec,1 Jean-Michel Brunel,2 Sarah Giacometti,1 Helene Maccario,3 Florian Correard,3 Eric Mas,3 Caroline Orneto,4 Ariel Savina,5 Fanny Bouquet,5 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino11SMARTc Unit, Pharmacokinetics Laboratory, CRCM UMR U1068 CNRS UMR 7258 Aix Marseille Un...

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Autores principales: Rodallec A, Brunel JM, Giacometti S, Maccario H, Correard F, Mas E, Orneto C, Savina A, Bouquet F, Lacarelle B, Ciccolini J, Fanciullino R
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
immunoliposomes – biopharmaceutical development –breast cancer – docetaxel - trastuzumab - HER2
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5e06676bf23b4bfa85b3f59357b9f471
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spelling oai:doaj.org-article:5e06676bf23b4bfa85b3f59357b9f4712021-12-02T00:19:16ZDocetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer1178-2013https://doaj.org/article/5e06676bf23b4bfa85b3f59357b9f4712018-06-01T00:00:00Zhttps://www.dovepress.com/docetaxel-trastuzumab-stealth-immunoliposome-development-and-in-vitro--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Anne Rodallec,1 Jean-Michel Brunel,2 Sarah Giacometti,1 Helene Maccario,3 Florian Correard,3 Eric Mas,3 Caroline Orneto,4 Ariel Savina,5 Fanny Bouquet,5 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino11SMARTc Unit, Pharmacokinetics Laboratory, CRCM UMR U1068 CNRS UMR 7258 Aix Marseille Université, Marseille, France; 2CRCM CNRS UMR 7258 Aix Marseille Université, Marseille, France; 3CRO2 UMR S_911 Aix Marseille Université, Marseille, France; 4Biopharmacy Laboratory, Aix Marseille Université, Marseille, France; 5Institut Roche, Boulogne Billancourt Cedex, FranceBackground: Trastuzumab plus docetaxel is a mainstay to treat HER2-positive breast cancers. However, developing nanoparticles could help to improve the efficacy/toxicity balance of this doublet by improving drug trafficking and delivery to tumors. This project aimed to develop an immunoliposome in breast cancer, combining docetaxel encapsulated in a stealth liposome engrafted with trastuzumab, and comparing its performances on human breast cancer cell lines with standard combination of docetaxel plus trastuzumab.Methods: Several strategies to engraft trastuzumab to pegylated liposomes were tested. Immunoliposomes made of natural (antibody nanoconjugate-1 [ANC-1]) and synthetic lipids (ANC-2) were synthesized using standard thin film method and compared in size, morphology, docetaxel encapsulation, trastuzumab engraftment rates and stability. Antiproliferative activity was tested on human breast cancer models ranging from almost negative (MDA-MB-231), positive (MDA-MB-453) to overexpressing (SKBR3) HER2. Finally, cell uptake of ANC-1 was studied by electronic microscopy.Results: ANC-1 showed a greater docetaxel encapsulation rate (73%±6% vs 53%±4%) and longer stability (up to 1 week) as compared with ANC-2. Both ANC presented particle size ≤150 nm and showed similar or higher in vitro antiproliferative activities than standard treatment, ANC-1 performing better than ANC-2. The IC50s for docetaxel combined to free trastuzumab were 8.7±4, 2±0.7 and 6±2 nM with MDA-MB-231, MDA-MB-453 and SKBR3, respectively. The IC50s for ANC-1 were 2.5±1, 1.8±0.6 and 3.4±0.8 nM and for ANC-2 were 1.8±0.3 nM, 2.8±0.8 nM and 6.8±1.8 nM with MDA-MB-231, MDA-MB-453 and SKBR3, respectively. Cellular uptake appeared to depend on HER2 expression, the higher the expression, the higher the uptake.Conclusion: In vitro results suggest that higher antiproliferative efficacy and efficient drug delivery can be achieved in breast cancer models using nanoparticles.Keywords: immunoliposomes, biopharmaceutical development, breast cancer, docetaxel, trastuzumab, HER2Rodallec ABrunel JMGiacometti SMaccario HCorreard FMas EOrneto CSavina ABouquet FLacarelle BCiccolini JFanciullino RDove Medical Pressarticleimmunoliposomes – biopharmaceutical development –breast cancer – docetaxel - trastuzumab - HER2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3451-3465 (2018)
institution DOAJ
collection DOAJ
language EN
topic immunoliposomes – biopharmaceutical development –breast cancer – docetaxel - trastuzumab - HER2
Medicine (General)
R5-920
spellingShingle immunoliposomes – biopharmaceutical development –breast cancer – docetaxel - trastuzumab - HER2
Medicine (General)
R5-920
Rodallec A
Brunel JM
Giacometti S
Maccario H
Correard F
Mas E
Orneto C
Savina A
Bouquet F
Lacarelle B
Ciccolini J
Fanciullino R
Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
description Anne Rodallec,1 Jean-Michel Brunel,2 Sarah Giacometti,1 Helene Maccario,3 Florian Correard,3 Eric Mas,3 Caroline Orneto,4 Ariel Savina,5 Fanny Bouquet,5 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino11SMARTc Unit, Pharmacokinetics Laboratory, CRCM UMR U1068 CNRS UMR 7258 Aix Marseille Université, Marseille, France; 2CRCM CNRS UMR 7258 Aix Marseille Université, Marseille, France; 3CRO2 UMR S_911 Aix Marseille Université, Marseille, France; 4Biopharmacy Laboratory, Aix Marseille Université, Marseille, France; 5Institut Roche, Boulogne Billancourt Cedex, FranceBackground: Trastuzumab plus docetaxel is a mainstay to treat HER2-positive breast cancers. However, developing nanoparticles could help to improve the efficacy/toxicity balance of this doublet by improving drug trafficking and delivery to tumors. This project aimed to develop an immunoliposome in breast cancer, combining docetaxel encapsulated in a stealth liposome engrafted with trastuzumab, and comparing its performances on human breast cancer cell lines with standard combination of docetaxel plus trastuzumab.Methods: Several strategies to engraft trastuzumab to pegylated liposomes were tested. Immunoliposomes made of natural (antibody nanoconjugate-1 [ANC-1]) and synthetic lipids (ANC-2) were synthesized using standard thin film method and compared in size, morphology, docetaxel encapsulation, trastuzumab engraftment rates and stability. Antiproliferative activity was tested on human breast cancer models ranging from almost negative (MDA-MB-231), positive (MDA-MB-453) to overexpressing (SKBR3) HER2. Finally, cell uptake of ANC-1 was studied by electronic microscopy.Results: ANC-1 showed a greater docetaxel encapsulation rate (73%±6% vs 53%±4%) and longer stability (up to 1 week) as compared with ANC-2. Both ANC presented particle size ≤150 nm and showed similar or higher in vitro antiproliferative activities than standard treatment, ANC-1 performing better than ANC-2. The IC50s for docetaxel combined to free trastuzumab were 8.7±4, 2±0.7 and 6±2 nM with MDA-MB-231, MDA-MB-453 and SKBR3, respectively. The IC50s for ANC-1 were 2.5±1, 1.8±0.6 and 3.4±0.8 nM and for ANC-2 were 1.8±0.3 nM, 2.8±0.8 nM and 6.8±1.8 nM with MDA-MB-231, MDA-MB-453 and SKBR3, respectively. Cellular uptake appeared to depend on HER2 expression, the higher the expression, the higher the uptake.Conclusion: In vitro results suggest that higher antiproliferative efficacy and efficient drug delivery can be achieved in breast cancer models using nanoparticles.Keywords: immunoliposomes, biopharmaceutical development, breast cancer, docetaxel, trastuzumab, HER2
format article
author Rodallec A
Brunel JM
Giacometti S
Maccario H
Correard F
Mas E
Orneto C
Savina A
Bouquet F
Lacarelle B
Ciccolini J
Fanciullino R
author_facet Rodallec A
Brunel JM
Giacometti S
Maccario H
Correard F
Mas E
Orneto C
Savina A
Bouquet F
Lacarelle B
Ciccolini J
Fanciullino R
author_sort Rodallec A
title Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
title_short Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
title_full Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
title_fullStr Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
title_full_unstemmed Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
title_sort docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/5e06676bf23b4bfa85b3f59357b9f471
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