Mechanism of cellular uptake of genotoxic silica nanoparticles

Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT...

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Main Authors:	Mu, Qingshan, Hondow, Nicole S, Krzemiński, Łukasz, Brown, Andy P, Jeuken, Lars JC, Routledge, Michael N
Format:	Online
Language:	English
Published:	BioMed Central 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479067/

id	pubmed-3479067
recordtype	oai_dc
spelling	pubmed-34790672012-10-24 Mechanism of cellular uptake of genotoxic silica nanoparticles Mu, Qingshan Hondow, Nicole S Krzemiński, Łukasz Brown, Andy P Jeuken, Lars JC Routledge, Michael N Research Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles. BioMed Central 2012-07-23 /pmc/articles/PMC3479067/ /pubmed/22823932 http://dx.doi.org/10.1186/1743-8977-9-29 Text en Copyright ©2012 Mu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mu, Qingshan Hondow, Nicole S Krzemiński, Łukasz Brown, Andy P Jeuken, Lars JC Routledge, Michael N
spellingShingle	Mu, Qingshan Hondow, Nicole S Krzemiński, Łukasz Brown, Andy P Jeuken, Lars JC Routledge, Michael N Mechanism of cellular uptake of genotoxic silica nanoparticles
author_facet	Mu, Qingshan Hondow, Nicole S Krzemiński, Łukasz Brown, Andy P Jeuken, Lars JC Routledge, Michael N
author_sort	Mu, Qingshan
title	Mechanism of cellular uptake of genotoxic silica nanoparticles
title_short	Mechanism of cellular uptake of genotoxic silica nanoparticles
title_full	Mechanism of cellular uptake of genotoxic silica nanoparticles
title_fullStr	Mechanism of cellular uptake of genotoxic silica nanoparticles
title_full_unstemmed	Mechanism of cellular uptake of genotoxic silica nanoparticles
title_sort	mechanism of cellular uptake of genotoxic silica nanoparticles
description	Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.
publisher	BioMed Central
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479067/
_version_	1611918237579083776

Mechanism of cellular uptake of genotoxic silica nanoparticles

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