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Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Heidegger Simon, Gößl Dorothée, Schmidt Alexandra, Niedermayer Stefan, Argyo Christian, Endres Stefan, Bein Thomas, Bourquin Carole,
Project RLR/TLR combination therapy: Mechanisms of T-cell recruitment into gastric tumors
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Original article (peer-reviewed)

Journal Nanoscale
Volume (Issue) 8(2)
Page(s) 938 - 948
Title of proceedings Nanoscale
DOI 10.1039/c5nr06122a

Open Access

URL https://arxiv.org/abs/1509.01029
Type of Open Access Repository (Green Open Access)

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.
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