Zimmer, Oliver and Walter, Melanie and Remmert, Marius and Maier, Olga and Witzgall, Ralph and Goepferich, Achim (2023) Impact of interferon-? on the target cell tropism of nanoparticles. JOURNAL OF CONTROLLED RELEASE, 362. pp. 325-341. ISSN 0168-3659, 1873-4995
Full text not available from this repository. (Request a copy)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-?.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; GAMMA-INTERFERON; IFN-GAMMA; CHOLESTEROL; CLEARANCE; UBIQUITINATION; CURVATURE; RECEPTORS; INFECTION; REDUCTASE; Targeted nanoparticles; Biodistribution; Preferential uptake; Targeting efficiency; Interferon-& gamma;; Cholesterol-25-hydroxylase (CH25H); Nano-bio interactions |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 600 Technology (Applied sciences) 600 Technology > 615 Pharmacy |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 06:39 |
| Last Modified: | 30 Jan 2024 06:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58974 |
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