Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

João P Barbosa,1–3,* Ana R Neves,3,* Andreia M Silva,1,2,4 Mário A Barbosa,1,2,4 M Salette Reis,3 Susana G Santos1,2 1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; 2INEB - Instit...

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Autores principales:	Barbosa JP, Neves AR, Silva AM, Barbosa MA, Reis MS, Santos SG
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	immunomodulation dendritic cell solid lipid nanoparticle imaging flow cytometry resveratrol TNF-a Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5244bba925ef4539953831b0ba2da203
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spelling	oai:doaj.org-article:5244bba925ef4539953831b0ba2da2032021-12-02T01:32:30ZNanostructured lipid carriers loaded with resveratrol modulate human dendritic cells1178-2013https://doaj.org/article/5244bba925ef4539953831b0ba2da2032016-07-01T00:00:00Zhttps://www.dovepress.com/nanostructured-lipid-carriers-loaded-with-resveratrol-modulate-human-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013João P Barbosa,1–3,* Ana R Neves,3,* Andreia M Silva,1,2,4 Mário A Barbosa,1,2,4 M Salette Reis,3 Susana G Santos1,2 1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; 2INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; 3UCIBIO, REQUIMTE, Chemical Sciences Department, Faculty of Pharmacy, University of Porto, Portugal; 4Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF-α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen – antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation. Keywords: immunomodulation, dendritic cell, solid lipid nanoparticle, imaging flow cytometry, resveratrol, TNF-α Barbosa JPNeves ARSilva AMBarbosa MAReis MSSantos SGDove Medical Pressarticleimmunomodulationdendritic cellsolid lipid nanoparticleimaging flow cytometryresveratrolTNF-aMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3501-3516 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunomodulation dendritic cell solid lipid nanoparticle imaging flow cytometry resveratrol TNF-a Medicine (General) R5-920
spellingShingle	immunomodulation dendritic cell solid lipid nanoparticle imaging flow cytometry resveratrol TNF-a Medicine (General) R5-920 Barbosa JP Neves AR Silva AM Barbosa MA Reis MS Santos SG Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
description	João P Barbosa,1–3,* Ana R Neves,3,* Andreia M Silva,1,2,4 Mário A Barbosa,1,2,4 M Salette Reis,3 Susana G Santos1,2 1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; 2INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; 3UCIBIO, REQUIMTE, Chemical Sciences Department, Faculty of Pharmacy, University of Porto, Portugal; 4Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF-α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen – antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation. Keywords: immunomodulation, dendritic cell, solid lipid nanoparticle, imaging flow cytometry, resveratrol, TNF-α
format	article
author	Barbosa JP Neves AR Silva AM Barbosa MA Reis MS Santos SG
author_facet	Barbosa JP Neves AR Silva AM Barbosa MA Reis MS Santos SG
author_sort	Barbosa JP
title	Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
title_short	Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
title_full	Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
title_fullStr	Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
title_full_unstemmed	Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
title_sort	nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/5244bba925ef4539953831b0ba2da203
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Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

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