title: Adjuvant properties of mesoporous silica particles tune the development of effector T cells.
abstract: 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 naïve 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 naïve 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.
authors.affiliation: Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helen
authors.initials: H
authors.lastname: Vallhov
authors.forename: Natalia
authors.initials: N
authors.lastname: Kupferschmidt
authors.forename: Susanne
authors.initials: S
authors.lastname: Gabrielsson
authors.forename: Staffan
authors.initials: S
authors.lastname: Paulie
authors.forename: Maria
authors.initials: M
authors.lastname: Strømme
authors.forename: Alfonso E
authors.initials: AE
authors.lastname: Garcia-Bennett
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D003713:Dendritic Cells / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D012822:Silicon Dioxide / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D000276:Adjuvants, Immunologic; D012822:Silicon Dioxide