title: Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery.
abstract: Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, 80336 Munich, Germany. carole.bourquin@unifr.ch and III. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany. bein@lmu.de.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Gössl
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany. bein@lmu.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany. bein@lmu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niedermayer
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany. bein@lmu.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Argyo
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, 80336 Munich, Germany. carole.bourquin@unifr.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany. bein@lmu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bein
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, 80336 Munich, Germany. carole.bourquin@unifr.ch and Chair of Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, 1700 Fribourg, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D017209:Apoptosis; D003102:Colloids / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007107:Immune System; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011108:Polymers; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry* / Q000276:immunology
chemical_list: D003102:Colloids; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D011108:Polymers; D018664:Interleukin-12; D012822:Silicon Dioxide; D016650:Fluorescein-5-isothiocyanate