Abstract
Interferon-? (IFN-?) is well known to reduce the infectivity of viral pathogens by altering their tissue tropism. This effect is induced by upregulation of cholesterol 25-hydroxylase (CH25H). Given the similarity of viral pathogens and ligand-functionalized nanoparticles in the underlying strategy of receptor-mediated cell recognition, it appears conceivable that IFN-? exceeds similar effects on ...
Abstract
Interferon-? (IFN-?) is well known to reduce the infectivity of viral pathogens by altering their tissue tropism. This effect is induced by upregulation of cholesterol 25-hydroxylase (CH25H). Given the similarity of viral pathogens and ligand-functionalized nanoparticles in the underlying strategy of receptor-mediated cell recognition, it appears conceivable that IFN-? exceeds similar effects on nanoparticles. Concretely, IFN-?-induced activation of CH25H could decrease nanoparticle avidity for target cells via depletion of clathrin-coated pits. We hypothesized that this effect would cause deterioration of target-cell specific accumulation of nanoparticles. To prove our hypothesis, we investigated the cell tropism of angiotensin II functionalized nanoparticles (NPLys-Ang II) in a co-culture system of angiotensin II subtype 1 receptor (AT(1)R) positive rat mesangial target cells (rMCs) and AT(1)R-negative HeLa off-target cells. In the presence of IFN-? we observed an up to 5-fold loss of target cell preference for NPLys-Ang II. Thus, our in vitro results suggest a strong influence of IFN-? on nanoparticle distribution, which is relevant in the context of nanotherapeutic approaches to cancer treatment, as IFN-? is strongly expressed in tumors. For the target cell tropism of viruses, our results provide a conclusive hypothesis for the underlying mechanism behind non-directed viral distribution in the presence of IFN-?.
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