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Efficient internalization of silica-coated iron oxide nanoparticles of different sizes by primary human macrophages and dendritic cells
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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2011 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 253, no 2, 81-93 p.Article in journal (Refereed) Published
Abstract [en]

Engineered nanoparticles are being considered for a wide range of biomedical applications, from magnetic resonance imaging to "smart" drug delivery systems. The development of novel nanomaterials for biomedical applications must be accompanied by careful scrutiny of their biocompatibility. In this regard, particular attention should be paid to the possible interactions between nanoparticles and cells of the immune system, our primary defense system against foreign invasion. On the other hand, labeling of immune cells serves as an ideal tool for visualization, diagnosis or treatment of inflammatory processes, which requires the efficient internalization of the nanoparticles into the cells of interest. Here, we compare novel monodispersed silica-coated iron oxide nanoparticles with commercially available dextran-coated iron oxide nanoparticles. The silica-coated iron oxide nanoparticles displayed excellent magnetic properties. Furthermore, they were nontoxic to primary human monocyte-derived macrophages at all doses tested whereas dose-dependent toxicity of the smaller silica-coated nanoparticles (30 nm and 50 nm) was observed for primary monocyte-derived dendritic cells, but not for the similarly small dextran-coated iron oxide nanoparticles. No macrophage or dendritic cell secretion of pro-inflammatory cytokines was observed upon administration of nanoparticles. The silica-coated iron oxide nanoparticles were taken up to a significantly higher degree when compared to the dextran-coated nanoparticles, irrespective of size. Cellular internalization of the silica-coated nanoparticles was through an active, actin cytoskeleton-dependent process. We conclude that these novel silica-coated iron oxide nanoparticles are promising materials for medical imaging, cell tracking and other biomedical applications. (C) 2011 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
2011. Vol. 253, no 2, 81-93 p.
Keyword [en]
Superparamagnetic nanoparticles, Surface coating, Biocompatibility, Cytokine secretion, Macrophages, Dendritic cells
National Category
Materials Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-35507DOI: 10.1016/j.taap.2011.03.011ISI: 000290822500001Scopus ID: 2-s2.0-79955636194OAI: oai:DiVA.org:kth-35507DiVA: diva2:428893
Note
QC 20110701Available from: 2011-07-01 Created: 2011-07-01 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Synthesis of nanostructured and hierarchical materials for bio-applications
Open this publication in new window or tab >>Synthesis of nanostructured and hierarchical materials for bio-applications
2011 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

In recent years, nanostructured materials incorporated with inorganic particles and polymers have attracted attention for simultaneous multifunctional biomedical applications. This thesis summarized three works, which are preparation of mesoporous silica coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles (NPs) as magnetic resonance imaging T2 contrast agents, polymer grafted Fe3O4@mSiO2 NPs response to temperature change, synthesis and biocompatibility evaluation of high aspect ratio (AR) gold nanorods.

Monodisperse Fe3O4@mSiO2 NPs have been prepared through a sol-gel process. The coating thickness and particle sizes can be precisely controlled by varying the synthesis parameters. Impact of surface coatings on magnetometric and relaxometric properties of Fe3O4 NPs is studied. The efficiency of these contrast agents, evaluated by MR relaxivities ratio (r2/r1), is much higher than that of the commercial ones. This coating-thickness dependent relaxation behavior is explained due to the effects of mSiO2 coatings on water exclusion.

Multifunctional core-shell composite NPs have been developed by growing thermo-sensitive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AAm)) on Fe3O4@mSiO2 NPs through free radical polymerization. Their phase transition behavior is studied, and their lower critical solution temperature (LCST) can be subtly tuned from ca. 34 to ca. 42 °C, suitable for further in vivo applications.

A seedless surfactant-mediated protocol has been applied for synthesis of high AR gold nanorods with the additive of HNO3. A growth mechanism based on the effect of nitrate ions on surfactant micelle elongation and Ostwald ripening process is proposed. The biocompatibility of high AR nanorods was evaluated on primary human monocyte derived dendritic cells (MDDCs). Their minor effects on viability and immune regulatory markers support further development for medical applications.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2011. x, 54 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2011:4
Keyword
Fe3O4, mSiO2, core-shell, MRI, multifunctional, PNIPAAm, LCST, gold, nanorod, nitric acid, AR, MDDC, biocompatibility, immunomodulation
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-35518 (URN)978-91-7415-903-5 (ISBN)
Presentation
2011-05-30, Sal C2, Isafjordsgatan 22, KTH, Stockholm, 14:00 (English)
Opponent
Supervisors
Note
QC 20110701Available from: 2011-07-01 Created: 2011-07-01 Last updated: 2011-09-29Bibliographically approved
2. Chemically Synthesized Nano-Structured Materials for Biomedical and Photonic Applications
Open this publication in new window or tab >>Chemically Synthesized Nano-Structured Materials for Biomedical and Photonic Applications
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanostructured materials have attracted a broad interest for applications in scientific and engineering fields due to their extraordinary properties stemming from the nanoscale dimensions. This dissertation presents the development of nanomaterials used for different applications, namely biomedicine and dye lasing.

Various inorganic nanoparticles have been developed as contrast agents for non-invasive medical imaging, such as magnetic resonance imaging (MRI) and X-ray computed tomography (CT), owing to their unique properties for efficient contrasting effect. Superparamagnetic iron oxide nanoparticles (SPIONs) are synthesized by thermo-decomposition method and phase-transferred to be hydrophilic used as MRI T2 (negative) contrast agents. Effects of surface modification of SPIONs by mesoporous silica (mSiO2) coating have been examined on the magnetic relaxivities. These contrast agents (Fe3O4@mSiO2) were found to have a coating-thickness dependent relaxation behavior and exhibit much higher contrast efficiency than that for the commercial ones. By growing thermo-sensitive poly(N-isopropylacrylamide -co-acrylamide) (P(NIPAAm-co-AAm)) as the outermost layer on Fe3O4@mSiO2 through free radical polymerization, a multifunctional core-shell nano-composite has been built up. Responding to the temperature change, these particles demonstrate phase transition behavior and were used for thermo-triggered magnetic separation. Their lower critical solution temperature (LCST) can be subtly tuned from ca. 34 to ca. 42 ˚C, suitable for further in vivo applications. An all-in-one contrast agent for MRI, CT and fluorescence imaging has been synthesized by depositing gadolinium oxide carbonate hydrate [Gd2O(CO3)2·H2O] shell on mSiO2-coated gold nanorod (Au NR), and then the particles were grafted with antibiofouling copolymer which can further link with the fluorescent dye. It shows both a higher CT and MRI contrast than the clinical iodine and gadolinium chelate contrast agent, respectively. Apart from the imaging application, owing to the morphology of Au NR, the particle has a plasmonic property of absorbing near-infrared (NIR) irradiation and suitable for future photothermal therapy. Cytotoxicity and biocompatibility of aforementioned nanoparticles have been evaluated and minor negative effects were found, which support their further development for medical applications.

Gold nanoparticles embedded in the optical gain material, water solution of Rhodamine 6G (Rh6G) in particular, used in dye lasers can both increase and damp the dye fluorescence, thus, changing the laser output intensity. The studies of size effect and coating of gold nanoparticles on photostability of the gain media reveal that small sized (ca. 5.5 nm) gold nanoparticles are found detrimental to the photostability, while for the larger ones (ca. 25 nm) fluorescence enhancement rather than quenching is likely to occur. And a noticeable improvement of the photostability for the gain material is achieved when gold is coated with SiO2.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. xii, 45 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2012:12
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-96261 (URN)
Public defence
2012-06-12, Sal/Hall C2, Electrum, KTH-ICT, Isafjordsgatan 26, Kista, 10:00 (English)
Opponent
Supervisors
Note
QC 20120605Available from: 2012-06-05 Created: 2012-05-31 Last updated: 2012-06-05Bibliographically approved

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