Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application

Catarina Costa Moura,1,2 Marcela A Segundo,1 José das Neves,3,4 Salette Reis,1 Bruno Sarmento3,4 1REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Faculty of Engineering, University of Porto, Porto, Portugal; 3CESPU, Instituto de Inv...

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Autores principales:	Moura CC, Segundo MA, das Neves J, Reis S, Sarmento B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1ff1ca29e11a48fba25a7e8a317e9040
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spelling	oai:doaj.org-article:1ff1ca29e11a48fba25a7e8a317e90402021-12-02T01:50:41ZCo-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application1178-2013https://doaj.org/article/1ff1ca29e11a48fba25a7e8a317e90402014-10-01T00:00:00Zhttp://www.dovepress.com/co-association-of-methotrexate-and-spions-into-anti-cd64-antibody-conj-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Catarina Costa Moura,1,2 Marcela A Segundo,1 José das Neves,3,4 Salette Reis,1 Bruno Sarmento3,4 1REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Faculty of Engineering, University of Porto, Porto, Portugal; 3CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto de Ciências da Saúde-Norte, Gandra PRD, Portugal; 4INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal Background: Rheumatoid arthritis (RA) is an autoimmune disease with severe consequences for the quality of life of sufferers. Regrettably, the inflammatory process involved remains unclear, and finding successful therapies as well as new means for its early diagnosis have proved to be daunting tasks. As macrophages are strongly associated with RA inflammation, effective diagnosis and therapy may encompass the ability to target these cells. In this work, a new approach for targeted therapy and imaging of RA was developed based on the use of multifunctional polymeric nanoparticles. Methods: Poly(lactic-co-glycolic acid) nanoparticles were prepared using a single emulsion-evaporation method and comprised the co-association of superparamagnetic iron oxide nanoparticles (SPIONs) and methotrexate. The nanoparticles were further functionalized with an antibody against the macrophage-specific receptor, CD64, which is overexpressed at sites of RA. The devised nanoparticles were characterized for mean particle size, polydispersity index, zeta potential, and morphology, as well as the association of SPIONs, methotrexate, and the anti-CD64 antibody. Lastly, the cytotoxicity of the developed nanoparticles was assessed in RAW 264.7 cells using standard MTT and LDH assays.Results: The nanoparticles had a mean diameter in the range of 130–200 nm and zeta potential values ranging from -32 mV to -16 mV. Association with either methotrexate or SPIONs did not significantly affect the properties of the nanoparticles. Conjugation with the anti-CD64 antibody, in turn, caused a slight increase in size and surface charge. Transmission electron microscopy confirmed the association of SPIONs within the poly(lactic-co-glycolic acid) matrix. Both anti-CD64 and methotrexate association were confirmed by Fourier transform infrared spectroscopy, and quantified yielding values as high as 36% and 79%, respectively. In vitro toxicity studies confirmed the methotrexate-loaded nanosystem to be more effective than the free drug.Conclusion: Multifunctional anti-CD64-conjugated poly(lactic-co-glycolic acid) nanoparticles for the combined delivery of methotrexate and SPIONs were successfully prepared and characterized. This nanosystem has the potential to provide a new theranostic approach for the management of RA. Keywords: FcγRI, methotrexate, poly(lactic-co-glycolic acid), superparamagnetic iron oxide nanoparticles, targeted drug deliveryMoura CCSegundo MAdas Neves JReis SSarmento BDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4911-4922 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Moura CC Segundo MA das Neves J Reis S Sarmento B Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
description	Catarina Costa Moura,1,2 Marcela A Segundo,1 José das Neves,3,4 Salette Reis,1 Bruno Sarmento3,4 1REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Faculty of Engineering, University of Porto, Porto, Portugal; 3CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto de Ciências da Saúde-Norte, Gandra PRD, Portugal; 4INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal Background: Rheumatoid arthritis (RA) is an autoimmune disease with severe consequences for the quality of life of sufferers. Regrettably, the inflammatory process involved remains unclear, and finding successful therapies as well as new means for its early diagnosis have proved to be daunting tasks. As macrophages are strongly associated with RA inflammation, effective diagnosis and therapy may encompass the ability to target these cells. In this work, a new approach for targeted therapy and imaging of RA was developed based on the use of multifunctional polymeric nanoparticles. Methods: Poly(lactic-co-glycolic acid) nanoparticles were prepared using a single emulsion-evaporation method and comprised the co-association of superparamagnetic iron oxide nanoparticles (SPIONs) and methotrexate. The nanoparticles were further functionalized with an antibody against the macrophage-specific receptor, CD64, which is overexpressed at sites of RA. The devised nanoparticles were characterized for mean particle size, polydispersity index, zeta potential, and morphology, as well as the association of SPIONs, methotrexate, and the anti-CD64 antibody. Lastly, the cytotoxicity of the developed nanoparticles was assessed in RAW 264.7 cells using standard MTT and LDH assays.Results: The nanoparticles had a mean diameter in the range of 130–200 nm and zeta potential values ranging from -32 mV to -16 mV. Association with either methotrexate or SPIONs did not significantly affect the properties of the nanoparticles. Conjugation with the anti-CD64 antibody, in turn, caused a slight increase in size and surface charge. Transmission electron microscopy confirmed the association of SPIONs within the poly(lactic-co-glycolic acid) matrix. Both anti-CD64 and methotrexate association were confirmed by Fourier transform infrared spectroscopy, and quantified yielding values as high as 36% and 79%, respectively. In vitro toxicity studies confirmed the methotrexate-loaded nanosystem to be more effective than the free drug.Conclusion: Multifunctional anti-CD64-conjugated poly(lactic-co-glycolic acid) nanoparticles for the combined delivery of methotrexate and SPIONs were successfully prepared and characterized. This nanosystem has the potential to provide a new theranostic approach for the management of RA. Keywords: FcγRI, methotrexate, poly(lactic-co-glycolic acid), superparamagnetic iron oxide nanoparticles, targeted drug delivery
format	article
author	Moura CC Segundo MA das Neves J Reis S Sarmento B
author_facet	Moura CC Segundo MA das Neves J Reis S Sarmento B
author_sort	Moura CC
title	Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
title_short	Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
title_full	Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
title_fullStr	Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
title_full_unstemmed	Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application
title_sort	co-association of methotrexate and spions into anti-cd64 antibody-conjugated plga nanoparticles for theranostic application
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/1ff1ca29e11a48fba25a7e8a317e9040
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Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application

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