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  • 1. Bondarenko, Olesja
    et al.
    Torres, Neus Feliu
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Garcia-Bennett, Alfonso
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Fadeel, Bengt
    Cellular uptake of mesoporous silica particles is governed by activation state of macrophages2014Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, s. S188-S188Artikkel i tidsskrift (Fagfellevurdert)
  • 2. Izquierdo-Barba, Isabel
    et al.
    Vallet-Regí, María
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Terasaki, Osamu
    Schmidtchen, Artur
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Incorporation of antimicrobial compounds in mesoporous silica film monolith2009Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, nr 29, s. 5729-5736Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Incorporation of the antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), as well as low molecular weight antimicrobial chlorhexidine, into mesoporous silica was obtained using an EISA one-pot synthesis method. FTIR confirmed efficient encapsulation of both LL-37 and chlorhexidine into mesoporous silica, while XRD and TEM showed that antimicrobial agent incorporation can be achieved without greatly affecting the structure of the mesoporous silica. The modified mesoporous silica released LL-37 and chlorhexidine slowly, reaching maximum release after about 200 h. The release rate could also be controlled through incorporation of SH groups in the pore walls, adding to pore hydrophobicity and reducing the release rate by about 50% compared to the unmodified mesoporous silica. Mesoporous silica containing either LL-37 or chlorhexidine displayed potent bactericidal properties against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. While chlorhexidine-loaded mesoporous silica displayed an accompanying high toxicity, as judged from hemolysis, LDH release, and MTT assay, the corresponding material containing LL-37 showed very low toxicity by all these assays, comparable to that observed for mesoporous silica in the absence of antibacterial drug, as well as to the negative controls in the respective assays. Mesoporous silica containing LL-37 therefore holds potential as an implantable material or a surface coating for such materials, as it combines potent bactericidal action with low toxicity, important features for controlling implant-related infections, e.g., for multi-resistant pathogens or for cases where access to the infection site of systemically administered antibiotics is limited due to collagen capsule formation or other factors.

  • 3.
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences2013Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

    Delarbeid
    1. 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
    Åpne denne publikasjonen i ny fane eller vindu >>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
    Vise andre…
    2009 (engelsk)Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 239, nr 3, s. 306-319Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Drug delivery, Endocytosis, Human monocyte-derived macrophages, Mesoporous silica particles, Programmed cell clearance
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-108064 (URN)10.1016/j.taap.2009.06.011 (DOI)000269677000011 ()19538981 (PubMedID)
    Tilgjengelig fra: 2009-09-04 Laget: 2009-09-04 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Adjuvant Properties of Mesoporous Silica Particles Tune the Development of Effector T Cells
    Åpne denne publikasjonen i ny fane eller vindu >>Adjuvant Properties of Mesoporous Silica Particles Tune the Development of Effector T Cells
    Vise andre…
    2012 (engelsk)Inngår i: Small, ISSN 1613-6810, Vol. 8, nr 13, s. 2116-2124Artikkel i tidsskrift (Fagfellevurdert) 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.

    sted, utgiver, år, opplag, sider
    John Wiley & Sons, 2012
    Emneord
    adjuvants, dendritic cells, immunology, mesoporous silica particles, naive T cells
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-179024 (URN)10.1002/smll.201102620 (DOI)000306011500021 ()
    Tilgjengelig fra: 2012-08-06 Laget: 2012-08-06 Sist oppdatert: 2016-11-30bibliografisk kontrollert
    3. Mesoporous silica particles potentiate antigen specific T cell responses
    Åpne denne publikasjonen i ny fane eller vindu >>Mesoporous silica particles potentiate antigen specific T cell responses
    Vise andre…
    2014 (engelsk)Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 12, s. 1835-1846Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-195901 (URN)10.2217/nnm.13.170 (DOI)000343904800006 ()
    Tilgjengelig fra: 2013-02-28 Laget: 2013-02-28 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. In vivo oral toxicological evaluation of mesoporous silica particles
    Åpne denne publikasjonen i ny fane eller vindu >>In vivo oral toxicological evaluation of mesoporous silica particles
    Vise andre…
    2013 (engelsk)Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 8, nr 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Mesoporous silica particles are highly promising nanomaterials for biomedical applications. They can be used to improve bioavailability, solubility and drug stability and to protect drugs from the acidic conditions of the stomach, leading to increased drug effectiveness. Their biocompatibility in vivo has recieved little attention, in particular regarding oral administration. Aim: To study the oral tolerance of micron-sized nanoporous folic acid-templated material-1 (cylindrical, 2D hexagonal pore structure) and nanometer-sized anionic-surfactant-templated mesoporous silica material-6 (cylindrical, 3D cubic pore structure) mesoporous silica particles in Sprague Dawley rats. Materials & methods: A dose stepwise procedure or range finding test was followed by a consequent confirmatory test. The confirmatory test included daily administrations of 2000 and 1200 mg/kg doses for nanoporous folic acid-templated material-1 and anionic-surfactant-templated mesoporous silica material-6, respectively. Results: The maximum tolerated dose for anionic-surfactant-templated mesoporous silica material-6 was not reached. Similar results were observed for nanometer-sized anionic-surfactant-templated mesoporous silica material-1 in most of the animals, although adverse effects were observed in some animals that are most probably due to the administration by oral gavage of the formulated particles. Conclusion: The results are promising for the use of mesoporous silica materials as drug-delivery systems in oral administration.

    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-180100 (URN)10.2217/nnm.12.77 (DOI)000314577800014 ()22891863 (PubMedID)
    Tilgjengelig fra: 2012-08-29 Laget: 2012-08-29 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    5. Large pore mesoporous silica induced weight loss in obese mice
    Åpne denne publikasjonen i ny fane eller vindu >>Large pore mesoporous silica induced weight loss in obese mice
    Vise andre…
    2013 (engelsk)Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 9, s. 1353-1362Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: There is a need for medical treatments to curb the rising rate of obesity. Weight reduction is correlated with a decrease in associated risk factors and cholesterol levels in humans. Amorphous silica particles have been found to exert a hypocholesterolemic effect in humans, making them popular dietary additives. Aim: To investigate the effect of mesoporous silica, which possess sharp pore size distributions, on: weight loss, cholesterol, triglycerides and glucose blood levels in obese mice. Materials & methods: Mesoporous silicas with differing pore size were mixed in the high-fat diet of obese mice. Results: Animals receiving large pore mesoporous silica with a high-fat diet show a significant reduction in body weight and fat composition, with no observable negative effects. Conclusion: Pore size is an important parameter for reduction of body weight and body fat composition by mesoporous silica, demonstrating promising signs for the treatment of obesity.

    Emneord
    body fat, body weight, cholesterol, high-fat diet, mesoporous silica, obesity
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-195903 (URN)10.2217/nnm.13.138 (DOI)000342071700012 ()24471500 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 2009-4716Novo NordiskSwedish Diabetes AssociationMagnus Bergvall FoundationCarl Tryggers foundation
    Tilgjengelig fra: 2013-02-28 Laget: 2013-02-28 Sist oppdatert: 2017-07-05bibliografisk kontrollert
  • 4.
    Kupferschmidt, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. Nanologica AB, SE-11428 Stockholm, Sweden.
    Csikasz, Robert
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Ballell, Lluis
    Diseases of the Developing World, GlaxoSmithKline, Madrid, Spanien.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Garcia-Bennett, Alfonso E.
    Stockholm Univ, Arrhenius Lab, MMK, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
    Large pore mesoporous silica induced weight loss in obese mice2013Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 9, s. 1353-1362Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is a need for medical treatments to curb the rising rate of obesity. Weight reduction is correlated with a decrease in associated risk factors and cholesterol levels in humans. Amorphous silica particles have been found to exert a hypocholesterolemic effect in humans, making them popular dietary additives. Aim: To investigate the effect of mesoporous silica, which possess sharp pore size distributions, on: weight loss, cholesterol, triglycerides and glucose blood levels in obese mice. Materials & methods: Mesoporous silicas with differing pore size were mixed in the high-fat diet of obese mice. Results: Animals receiving large pore mesoporous silica with a high-fat diet show a significant reduction in body weight and fat composition, with no observable negative effects. Conclusion: Pore size is an important parameter for reduction of body weight and body fat composition by mesoporous silica, demonstrating promising signs for the treatment of obesity.

  • 5.
    Kupferschmidt, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Garcia-Bennett, Alfonso
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Biocompatibility and Immunological Evaluation of Mesoporous Silica for use as Potential Adjuvants.2012Inngår i: Materials for Tomorrow, 2012Konferansepaper (Fagfellevurdert)
  • 6.
    Kupferschmidt, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Rahman Qazi, Khaleda
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Kemi, Cecilia
    Vallhov, Helen
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Garcia-Bennett, Alfonso E
    Stockholm Univ, Dept Mat & Environm Chem, Stockholm, Sweden.
    Gabrielsson, Susanne
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Scheynius, Annika
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Mesoporous silica particles potentiate antigen specific T cell responses2014Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 12, s. 1835-1846Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Kupferschmidt, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Dendritic Cells Exposed to Mesoporous Silica Particles Tune the Development of Naïve T Cells into Different Effector Cells2011Inngår i: MRS 2011 Spring meeting San Francisco: Hybrid Biological Materials I, JJ3.16, 2011Konferansepaper (Fagfellevurdert)
  • 8.
    Kupferschmidt, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Xia, Xin
    Nanologica AB, Stockholm, och Dept of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University.
    Labrador, Roberto H
    Nanologica AB, Stockholm, Sweden.
    Atluri, Rambabu
    Nanologica AB, Stockholm, Sweden.
    Ballell, Lluis
    Diseases of the Developing World, GlaxoSmithKline, Madrid, Spanien.
    Garcia-Bennett, Alfonso E
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    In vivo oral toxicological evaluation of mesoporous silica particles2013Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 8, nr 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Mesoporous silica particles are highly promising nanomaterials for biomedical applications. They can be used to improve bioavailability, solubility and drug stability and to protect drugs from the acidic conditions of the stomach, leading to increased drug effectiveness. Their biocompatibility in vivo has recieved little attention, in particular regarding oral administration. Aim: To study the oral tolerance of micron-sized nanoporous folic acid-templated material-1 (cylindrical, 2D hexagonal pore structure) and nanometer-sized anionic-surfactant-templated mesoporous silica material-6 (cylindrical, 3D cubic pore structure) mesoporous silica particles in Sprague Dawley rats. Materials & methods: A dose stepwise procedure or range finding test was followed by a consequent confirmatory test. The confirmatory test included daily administrations of 2000 and 1200 mg/kg doses for nanoporous folic acid-templated material-1 and anionic-surfactant-templated mesoporous silica material-6, respectively. Results: The maximum tolerated dose for anionic-surfactant-templated mesoporous silica material-6 was not reached. Similar results were observed for nanometer-sized anionic-surfactant-templated mesoporous silica material-1 in most of the animals, although adverse effects were observed in some animals that are most probably due to the administration by oral gavage of the formulated particles. Conclusion: The results are promising for the use of mesoporous silica materials as drug-delivery systems in oral administration.

  • 9. Vallhov, H.
    et al.
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Garcia-Bennett, Alfonso E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gabrielsson, S.
    Scheynius, A.
    Mesoporous silica particles: Potential delivery system and immunomodulatory adjuvant2009Konferansepaper (Fagfellevurdert)
  • 10. Vallhov, H
    et al.
    Kupherschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gabrielsson, S
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Scheynius, A
    Garcia- Bennett, Alfonso
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Immunomodulatory responses triggered by mesoporous silica particles: A study on human dendritic cells2008Konferansepaper (Fagfellevurdert)
  • 11.
    Vallhov, Helen
    et al.
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gabrielsson, Susanne
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Paulie, Staffan
    Mabtech AB, Nacka Strand, Sweden.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Garcia-Bennett, Alfonso E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Scheynius, Annika
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Adjuvant Properties of Mesoporous Silica Particles Tune the Development of Effector T Cells2012Inngår i: Small, ISSN 1613-6810, Vol. 8, nr 13, s. 2116-2124Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 12. Witasp, Erika
    et al.
    Kupferschmidt, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Bengtsson, Linnéa
    Hultenby, Kjell
    Smedman, Christian
    Paulie, Staffan
    Garcia-Bennett, Alfonso E
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Fadeel, Bengt
    Efficient internalization of mesoporous silica particles of different sizes by primary human macrophages without impairment of macrophage clearance of apoptotic or antibody-opsonized target cells2009Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 239, nr 3, s. 306-319Artikkel i tidsskrift (Fagfellevurdert)
    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.

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