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Efficient internalization of mesoporous silica particles of different sizes by primary human macrophages without impairment of macrophage clearance of apoptotic or antibody-opsonized target cells
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanoteknologi och funktionella material)
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2009 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 239, no 3, 306-319 p.Article in journal (Refereed) Published
Abstract [en]

Macrophage recognition and ingestion of apoptotic cell corpses, a process referred to as programmed cell clearance, is of considerable importance for the maintenance of tissue homeostasis and in the resolution of inflammation. Moreover, macrophages are the first line of defense against microorganisms and other foreign materials including particles. However, there is sparse information on the mode of uptake of engineered nanomaterials by primary macrophages. In this study, mesoporous silica particles with cubic pore geometries and covalently fluorescein-grafted particles were synthesized through a novel route, and their interactions with primary human monocyte-derived macrophages were assessed. Efficient and active internalization of mesoporous silica particles of different sizes was observed by transmission electron microscopic and flow cytometric analysis and studies using pharmacological inhibitors suggested that uptake occurred through a process of endocytosis. Moreover, uptake of silica particles was independent of serum factors. The silica particles with very high surface areas due to their porous structure did not impair cell viability or function of macrophages, including the ingestion of different classes of apoptotic or opsonized target cells. The current findings are relevant to the development of mesoporous materials for drug delivery and other biomedical applications.

Place, publisher, year, edition, pages
2009. Vol. 239, no 3, 306-319 p.
Keyword [en]
Drug delivery, Endocytosis, Human monocyte-derived macrophages, Mesoporous silica particles, Programmed cell clearance
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
URN: urn:nbn:se:uu:diva-108064DOI: 10.1016/j.taap.2009.06.011ISI: 000269677000011PubMedID: 19538981OAI: oai:DiVA.org:uu-108064DiVA: diva2:234146
Available from: 2009-09-04 Created: 2009-09-04 Last updated: 2016-04-14Bibliographically approved
In thesis
1. Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
Open this publication in new window or tab >>Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mesoporous silica particles offer great potential benefits as vehicles for drug delivery and in other biomedical applications. They present a high loading capacity due their ordered and size-tuneable pores that allow molecules to be loaded and released. In addition, they offer the possibility to enhance oral bioavailability of drugs with limited aqueous solubility and to protect pH sensitive drugs from the acidic conditions in the stomach on their way to the intestine.

The aim of this thesis was to evaluate the biocompatibility and effects of mesoporous silica particles on immunocompetent cells. Subsequently, two potential life sciences applications were investigated: as adjuvants and as weight reduction agents.

Adjuvants are used in vaccines in order to enhance the immunological response towards attenuated and poorly immunogenic antigens. Their function can be mediated through dendritic cells which have a central role in the control of adaptive immunity including immunological memory. Our results show that different types of mesoporous silica particles were able to tune the development of T cells both in human cell cultures and in mice. In contrast to the approved adjuvant alum (aluminium salts) which is a specific inducer of Th2-type immune responses, the particles induced more Th1-like responses, which may be desired in vaccines against allergy and intracellular pathogens such as viruses. Particle exposure to macrophages did not affect their cell function which is crucial for tissue homeostasis, wound repair and in prevention of autoimmune responses. Likewise, the cytokine secretion was not affected, which suggest that macrophages would not modulate the immune response towards the particles.

Furthermore, mesoporous silica particles were highly tolerated at daily oral administrations of up to 2000 mg/kg doses for some of the materials prepared. Large pore mesoporous silica particles were shown to act as weight and body fat reduction agents without other observable pathological signs when administered in the diet of obese mice.

Together; those results are promising for the development of mesoporous silica as drug delivery systems and adjuvants for oral administration of drugs or vaccines. Additionally, large pore mesoporous silica materials are potential agents for the treatment of obesity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 76 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1023
mesoporous silica, biocompatibility, adjuvants, drug delivery systems, obesity
National Category
Nano Technology
urn:nbn:se:uu:diva-195904 (URN)978-91-554-8605-1 (ISBN)
Public defence
2013-04-11, Polhemssalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 14:00 (English)
Available from: 2013-03-21 Created: 2013-02-28 Last updated: 2013-05-02Bibliographically approved

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Kupferschmidt, NataliaGarcia-Bennett, Alfonso E
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