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Adjuvant Properties of Mesoporous Silica Particles Tune the Development of Effector T Cells
Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
Mabtech AB, Nacka Strand, Sweden.
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2012 (English)In: Small, ISSN 1613-6810, Vol. 8, no 13, 2116-2124 p.Article in journal (Refereed) Published
Abstract [en]

Alum is the most frequently used adjuvant today, primarily inducing Th2 responses. However, Th1-type responses are often desirable within immune therapy, and therefore the development of new adjuvants is greatly needed. Mesoporous silica particles with a highly ordered pore structure have properties that make them very interesting for future controlled drug delivery systems, such as controllable particle and pore size; they also have the ability to induce minor immune modulatory effects, as previously demonstrated on human-monocyte-derived dendritic cells (MDDCs). In this study, mesoporous silica particles are shown to be efficiently engulfed by MDDCs within 2 h, probably by phagocytic uptake, as seen by confocal microscopy and transmission electron microscopy. A co-culture protocol is developed to evaluate the capability of MDDCs to stimulate the development of naive CD4+ T cells in different directions. The method, involving ELISpot as a readout system, demonstrates that MDDCs, after exposure to mesoporous silica particles (AMS-6 and SBA-15), are capable of tuning autologous naive T cells into different effector cells. Depending on the size and functionalization of the particles added to the cells, different cytokine patterns are detected. This suggests that mesoporous silica particles can be used as delivery vehicles with tunable adjuvant properties, which may be of importance for several medical applications, such as immune therapy and vaccination.

Place, publisher, year, edition, pages
John Wiley & Sons, 2012. Vol. 8, no 13, 2116-2124 p.
Keyword [en]
adjuvants, dendritic cells, immunology, mesoporous silica particles, naive T cells
National Category
Engineering and Technology Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
URN: urn:nbn:se:uu:diva-179024DOI: 10.1002/smll.201102620ISI: 000306011500021OAI: oai:DiVA.org:uu-179024DiVA: diva2:543100
Available from: 2012-08-06 Created: 2012-08-06 Last updated: 2013-03-22Bibliographically 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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