Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC...

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Main Authors: Besic Gyenge Emina, Darphin Xenia, Wirth Amina, Pieles Uwe, Walt Heinrich, Bredell Marius, Maake Caroline
Format: Article
Language:English
Published: BMC 2011-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://www.jnanobiotechnology.com/content/9/1/32
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author Besic Gyenge Emina
Darphin Xenia
Wirth Amina
Pieles Uwe
Walt Heinrich
Bredell Marius
Maake Caroline
author_facet Besic Gyenge Emina
Darphin Xenia
Wirth Amina
Pieles Uwe
Walt Heinrich
Bredell Marius
Maake Caroline
author_sort Besic Gyenge Emina
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO<sub>2</sub>-OH, Ru@SiO<sub>2</sub>-NH<sub>2</sub>, Ru@SiO<sub>2</sub>-PEG) in the human HNSCC cell line UMB-SCC 745.</p> <p>Results</p> <p>We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>uptake of Ru@SiO<sub>2</sub>-PEG was minimal even after 24 h.</p> <p>Conclusions</p> <p>Our study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.</p>
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spelling doaj.art-8fe2b12296364706b2b349bbe77f2fe72022-12-22T02:20:41ZengBMCJournal of Nanobiotechnology1477-31552011-08-01913210.1186/1477-3155-9-32Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinomaBesic Gyenge EminaDarphin XeniaWirth AminaPieles UweWalt HeinrichBredell MariusMaake Caroline<p>Abstract</p> <p>Background</p> <p>Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO<sub>2</sub>-OH, Ru@SiO<sub>2</sub>-NH<sub>2</sub>, Ru@SiO<sub>2</sub>-PEG) in the human HNSCC cell line UMB-SCC 745.</p> <p>Results</p> <p>We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO<sub>2</sub>-OH and Ru@SiO<sub>2</sub>-NH<sub>2 </sub>uptake of Ru@SiO<sub>2</sub>-PEG was minimal even after 24 h.</p> <p>Conclusions</p> <p>Our study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.</p>http://www.jnanobiotechnology.com/content/9/1/32nanoparticlessilica dioxidesurface propertiestumor cell lineuptakeendocytosiscellular fate
spellingShingle Besic Gyenge Emina
Darphin Xenia
Wirth Amina
Pieles Uwe
Walt Heinrich
Bredell Marius
Maake Caroline
Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
Journal of Nanobiotechnology
nanoparticles
silica dioxide
surface properties
tumor cell line
uptake
endocytosis
cellular fate
title Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
title_full Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
title_fullStr Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
title_full_unstemmed Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
title_short Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
title_sort uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma
topic nanoparticles
silica dioxide
surface properties
tumor cell line
uptake
endocytosis
cellular fate
url http://www.jnanobiotechnology.com/content/9/1/32
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AT wirthamina uptakeandfateofsurfacemodifiedsilicananoparticlesinheadandnecksquamouscellcarcinoma
AT pielesuwe uptakeandfateofsurfacemodifiedsilicananoparticlesinheadandnecksquamouscellcarcinoma
AT waltheinrich uptakeandfateofsurfacemodifiedsilicananoparticlesinheadandnecksquamouscellcarcinoma
AT bredellmarius uptakeandfateofsurfacemodifiedsilicananoparticlesinheadandnecksquamouscellcarcinoma
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