Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Orlando A, Re F, Sesana S, Rivolta I, Panariti A, Brambilla D, Nicolas J, Couvreur P, Andrieux K, Masserini M, Cazzaniga E.
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://doaj.org/article/5865e72ef76f42659f34d9b6eea8272d
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:5865e72ef76f42659f34d9b6eea8272d
record_format dspace
spelling oai:doaj.org-article:5865e72ef76f42659f34d9b6eea8272d2021-12-02T01:50:38ZEffect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages1176-91141178-2013https://doaj.org/article/5865e72ef76f42659f34d9b6eea8272d2013-04-01T00:00:00Zhttp://www.dovepress.com/effect-of-nanoparticles-binding-szlig-amyloid-peptide-on-nitric-oxide--a12770https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud, University Paris-Sud, Châtenay-Malabry, France Background: As part of a project designing nanoparticles for the treatment of Alzheimer’s disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate) nanoparticles (PEG-PACA). We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL), together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in both cell lines, starting at the lowest dose (10 µg/mL), with increased production of nitric oxide detected only at the highest dose (1500 µg/mL). Exposure to PEG-PACA affected cell viability and production of nitric oxide in both cell lines, but only at the highest concentration (640 µg/mL). Conclusion: Liposomal and PEG-PACA nanoparticles have a limited effect on vascular homeostasis and inflammatory response, rendering them potentially suitable for treatment of Alzheimer’s disease. Moreover, they highlight the importance of testing such nanoparticles for production of nitric oxide in vitro in order to identify a therapeutic dose range suitable for use in vivo. Keywords: nanoparticles, nitric oxide, endothelial cells, macrophages, Alzheimer’s diseaseOrlando ARe FSesana SRivolta IPanariti ABrambilla DNicolas JCouvreur PAndrieux KMasserini MCazzaniga E.Dove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1335-1347 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Orlando A
Re F
Sesana S
Rivolta I
Panariti A
Brambilla D
Nicolas J
Couvreur P
Andrieux K
Masserini M
Cazzaniga E.
Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
description Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud, University Paris-Sud, Châtenay-Malabry, France Background: As part of a project designing nanoparticles for the treatment of Alzheimer’s disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate) nanoparticles (PEG-PACA). We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL), together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in both cell lines, starting at the lowest dose (10 µg/mL), with increased production of nitric oxide detected only at the highest dose (1500 µg/mL). Exposure to PEG-PACA affected cell viability and production of nitric oxide in both cell lines, but only at the highest concentration (640 µg/mL). Conclusion: Liposomal and PEG-PACA nanoparticles have a limited effect on vascular homeostasis and inflammatory response, rendering them potentially suitable for treatment of Alzheimer’s disease. Moreover, they highlight the importance of testing such nanoparticles for production of nitric oxide in vitro in order to identify a therapeutic dose range suitable for use in vivo. Keywords: nanoparticles, nitric oxide, endothelial cells, macrophages, Alzheimer’s disease
format article
author Orlando A
Re F
Sesana S
Rivolta I
Panariti A
Brambilla D
Nicolas J
Couvreur P
Andrieux K
Masserini M
Cazzaniga E.
author_facet Orlando A
Re F
Sesana S
Rivolta I
Panariti A
Brambilla D
Nicolas J
Couvreur P
Andrieux K
Masserini M
Cazzaniga E.
author_sort Orlando A
title Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
title_short Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
title_full Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
title_fullStr Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
title_full_unstemmed Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
title_sort effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/5865e72ef76f42659f34d9b6eea8272d
work_keys_str_mv AT orlandoa effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT ref effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT sesanas effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT rivoltai effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT panaritia effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT brambillad effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT nicolasj effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT couvreurp effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT andrieuxk effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT masserinim effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
AT cazzanigae effectofnanoparticlesbindingszligamyloidpeptideonnitricoxideproductionbyculturedendothelialcellsandmacrophages
_version_ 1718402837327642624