Remmert, Marius and Konrad, Johannes and Birringer, Jan and Goepferich, Achim (2025) Interferon gamma modifies nanoparticle tropism and cell uptake. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 113: 107301. ISSN 1773-2247, 2588-8943
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Interferon gamma (IFN-gamma) challenges the ability of viruses to distinguish between target and off-target cells i.e. viral tropism. Due to the similarity of viruses and nanoparticles in shape and size, we hypothesized that the effect of IFN-gamma on viruses also applies to virus-mimetic nanoparticles. Therefore, we determined the influence of IFN-gamma on nanoparticle tropism and cell uptake. For our experiments, we used cyclic RGD-peptide (cRGD) functionalized polymeric nanoparticles and lipid nanocapsules (LNC) to target the alpha v beta 3 integrin receptor on cell membranes of rat mesangial cells (rMCs), HeLa cells and human dermal microvascular endothelial cells (HDMEC). We used a nanoparticle concentration range between 0.1 and 2 nM. The IFN-gamma concentrations and IFN-gamma incubation times varied in the range of 100 IU-1000 IU and zero to 54 h respectively. When we measured nanoparticle uptake via flow cytometry 24 h after cytokine administration to cells, our findings confirmed that IFN-gamma decreased the tropism as well as the uptake of functionalized nanoparticles by target cells. We were able to demonstrate a maximal IFN gamma effect at a concentration of 100 IU of IFN-gamma and a 24-h incubation time. The presence of IFN-gamma is associated with an upregulation of cholesterol 25-hydroxylase (CH25H). That the CH25H oxidation product, 25-hydroxycholesterol (25HC), is known to inhibit cell-nanoparticle interactions points at the potentially underlying mechanism of the observed INF-gamma effect.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; IFN-GAMMA; 25-HYDROXYCHOLESTEROL; EXPRESSION; CLEARANCE; DETERMINANTS; REDUCTION; ENTRY; HIV-1; Interferon-gamma effect; Nanoparticle uptake; Nanoparticle tropism; Cholesterol content; Targeting efficiency |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jun 2026 06:07 |
| Last Modified: | 18 Jun 2026 06:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66028 |
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