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Zeiringer, S; Derler, M; Mussbacher, M; Kolesnik, T; Fröhlich, E; Leitinger, G; Kolb, D; Tutz, S; Vargas, C; Keller, S; Roblegg, E.
Immune Modulation with Nanodiscs: Surface Charge Dictates Cellular Interactions and Activation of Macrophages and Dendritic-like Cells
INT J MOL SCI. 2025; 26(11): 5154
Doi: 10.3390/ijms26115154
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- Co-authors Med Uni Graz
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Fröhlich Eleonore
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Kolb Dagmar
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Kolesnik Tatjana
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Leitinger Gerd
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- Abstract:
- The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene-maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc-cell interaction studies-including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression-demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.
- Find related publications in this database (Keywords)
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monocyte differentiation
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macrophages
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immature dendritic-like cells
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in vitro immune model
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nanodiscs
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immune response modulation
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immune cell activation