Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells

Fernando Rodríguez-Serrano,1,* Nuria Mut-Salud,1,* Teresa Cruz-Bustos,2 Mercedes Gomez-Samblas,2 Esther Carrasco,1 Jose Manuel Garrido,3 F Javier López-Jaramillo,4 Francisco Santoyo-Gonzalez,4 Antonio Osuna2 1Institute of Biopathology and Regenerative Medicine, 2Molecular Bioc...

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Autores principales:	Rodríguez-Serrano F, Mut-Salud N, Cruz-Bustos T, Gomez-Samblas M, Carrasco E, Garrido JM, López-Jaramillo FJ, Santoyo-Gonzalez F, Osuna A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	targeted drug delivery doxorubicin HER2 nanoparticle paclitaxel protein A trastuzumab Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8b769a1a364c4f0a87fa343c7c143d50
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spelling	oai:doaj.org-article:8b769a1a364c4f0a87fa343c7c143d502021-12-02T00:45:22ZFunctionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells1178-2013https://doaj.org/article/8b769a1a364c4f0a87fa343c7c143d502016-09-01T00:00:00Zhttps://www.dovepress.com/functionalized-immunostimulating-complexes-with-protein-a-via-lipid-vi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fernando Rodríguez-Serrano,1,* Nuria Mut-Salud,1,* Teresa Cruz-Bustos,2 Mercedes Gomez-Samblas,2 Esther Carrasco,1 Jose Manuel Garrido,3 F Javier López-Jaramillo,4 Francisco Santoyo-Gonzalez,4 Antonio Osuna2 1Institute of Biopathology and Regenerative Medicine, 2Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Faculty of Sciences, Institute of Biotechnology, University of Granada, 3Department of Cardiovascular Surgery, Virgen de las Nieves Hospital, 4Department of Organic Chemistry, Faculty of Sciences, Institute of Biotechnology, University of Granada, Granada, Spain *These authors contributed equally to this work Background: Around 20%–30% of breast cancers overexpress the proto-oncogene human epidermal growth receptor 2 (HER2), and they are characterized by being very invasive. Therefore, many current studies are focused on testing new therapies against tumors that overexpress this receptor. In particular, there exists major interest in new strategies to fight breast cancer resistant to trastuzumab (Tmab), a humanized antibody that binds specifically to HER2 interfering with its mitogenic signaling. Our team has previously developed immunostimulating complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones, which can incorporate protein A and bind to G immunoglobulins that makes them very flexible nanocarriers.Methods and results: The aim of this in vitro study was to synthesize and evaluate a drug delivery system based on protein A-functionalized ISCOMs to target HER2-overexpressing cells. We describe the preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non-overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy. Results show that the uptake is dependent on the level of overexpression of HER2, and the analysis of the cell viability reveals that targeted drugs are selective toward HCC1954, whereas MCF-7 cells remain unaffected.Conclusion: Protein A-functionalized ISCOMs are versatile carriers that can be coupled to antibodies that act as targeting agents to deliver drugs. When coupling to Tmab and loading with paclitaxel or doxorubicin, they become efficient vehicles for the selective delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells. These nanoparticles may pave the way for the development of novel therapies for poor prognosis resistant patients. Keywords: targeted drug delivery, doxorubicin, HER2, nanoparticle, paclitaxel, protein A, trastuzumabRodríguez-Serrano FMut-Salud NCruz-Bustos TGomez-Samblas MCarrasco EGarrido JMLópez-Jaramillo FJSantoyo-Gonzalez FOsuna ADove Medical Pressarticletargeted drug deliverydoxorubicinHER2nanoparticlepaclitaxelprotein AtrastuzumabMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4777-4785 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	targeted drug delivery doxorubicin HER2 nanoparticle paclitaxel protein A trastuzumab Medicine (General) R5-920
spellingShingle	targeted drug delivery doxorubicin HER2 nanoparticle paclitaxel protein A trastuzumab Medicine (General) R5-920 Rodríguez-Serrano F Mut-Salud N Cruz-Bustos T Gomez-Samblas M Carrasco E Garrido JM López-Jaramillo FJ Santoyo-Gonzalez F Osuna A Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
description	Fernando Rodríguez-Serrano,1,* Nuria Mut-Salud,1,* Teresa Cruz-Bustos,2 Mercedes Gomez-Samblas,2 Esther Carrasco,1 Jose Manuel Garrido,3 F Javier López-Jaramillo,4 Francisco Santoyo-Gonzalez,4 Antonio Osuna2 1Institute of Biopathology and Regenerative Medicine, 2Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Faculty of Sciences, Institute of Biotechnology, University of Granada, 3Department of Cardiovascular Surgery, Virgen de las Nieves Hospital, 4Department of Organic Chemistry, Faculty of Sciences, Institute of Biotechnology, University of Granada, Granada, Spain *These authors contributed equally to this work Background: Around 20%–30% of breast cancers overexpress the proto-oncogene human epidermal growth receptor 2 (HER2), and they are characterized by being very invasive. Therefore, many current studies are focused on testing new therapies against tumors that overexpress this receptor. In particular, there exists major interest in new strategies to fight breast cancer resistant to trastuzumab (Tmab), a humanized antibody that binds specifically to HER2 interfering with its mitogenic signaling. Our team has previously developed immunostimulating complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones, which can incorporate protein A and bind to G immunoglobulins that makes them very flexible nanocarriers.Methods and results: The aim of this in vitro study was to synthesize and evaluate a drug delivery system based on protein A-functionalized ISCOMs to target HER2-overexpressing cells. We describe the preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non-overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy. Results show that the uptake is dependent on the level of overexpression of HER2, and the analysis of the cell viability reveals that targeted drugs are selective toward HCC1954, whereas MCF-7 cells remain unaffected.Conclusion: Protein A-functionalized ISCOMs are versatile carriers that can be coupled to antibodies that act as targeting agents to deliver drugs. When coupling to Tmab and loading with paclitaxel or doxorubicin, they become efficient vehicles for the selective delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells. These nanoparticles may pave the way for the development of novel therapies for poor prognosis resistant patients. Keywords: targeted drug delivery, doxorubicin, HER2, nanoparticle, paclitaxel, protein A, trastuzumab
format	article
author	Rodríguez-Serrano F Mut-Salud N Cruz-Bustos T Gomez-Samblas M Carrasco E Garrido JM López-Jaramillo FJ Santoyo-Gonzalez F Osuna A
author_facet	Rodríguez-Serrano F Mut-Salud N Cruz-Bustos T Gomez-Samblas M Carrasco E Garrido JM López-Jaramillo FJ Santoyo-Gonzalez F Osuna A
author_sort	Rodríguez-Serrano F
title	Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
title_short	Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
title_full	Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
title_fullStr	Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
title_full_unstemmed	Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells
title_sort	functionalized immunostimulating complexes with protein a via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant her2-overexpressing breast cancer cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/8b769a1a364c4f0a87fa343c7c143d50
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Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells

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