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%0 Thesis
%A Lin, Cheng
%T Exploring the interaction of lipid nanoparticles and tattoo pigments with macrophages
%I Rheinisch-Westfälische Technische Hochschule Aachen
%V Dissertation
%C Aachen
%M RWTH-2025-04992
%P 39, 19 Seiten : Illustrationen
%D 2025
%Z Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2025, Kumulative Dissertation
%X Macrophages are essential cells in the innate immune system, known for their potent phagocytosis and antigen presentation. They play a key role in pathogen defense, tissue repair, inflammation regulation, and metabolic homeostasis. Macrophages also play a role for the uptake and persistence of tattoo ink in the skin, and a suitable 3D model for human skin would provide insights into the mechanisms underlying the cellular distribution of tattoo ink. Understanding macrophage function and reprogramming them using appropriate substances is crucial for advancing treatment of inflammatory diseases and cancer. Lipid nanoparticles (LNPs) are nano-scaled carriers that enable delivery of therapeutic nucleic acids like mRNA, siRNA, and plasmid-DNA. LNPs have gained prominence in drug delivery, especially in mRNA-based COVID-19 vaccines. Recent research shows LNPs predominantly accumulate in the liver following intravenous injection, offering therapeutic potential for liver diseases. However, the rapid hepatic clearance of LNPs limits their efficacy. To address this, noninvasive hybrid microcomputed fluorescence molecular tomography (CT-FLT) and flow cytometry were conducted with C57BL6/J wild-type control mice, Low-density lipoprotein receptor (Ldlr)−/− mice, treated with leukotriene B4 receptor inhibitor (BLT1i) or small molecule-based High-density lipoprotein receptor inhibitor (HDLRi) and which were then all treated with siRNA-LNPs. The imaging study indicated that BLT1i enhanced hepatic uptake of siRNA-LNPs, while the HDLRi reduced liver uptake and redirected siRNA to immune cells in the spleen and blood as shown by flow cytometry. This underscores the potential of HDLRi for extrahepatic and immune-targeted siRNA delivery. In collaboration with the Clinic for Dermatology and Allergology of the university hospital Aachen, a 3D skin model consisting of keratinocytes, fibroblasts, and macrophages was developed to study the cellular distribution of tattoo ink in skin cells. In addition, we studied the effects of tattoo ink on human primary leukocytes. We found that human macrophages were most effective in internalizing ink in full-thickness 3D skin models. Macrophage cultures showed that the ink did not induce elevated inflammatory mediators and showed no signs of toxicity, even after nine days. Notably, monocytes were most efficient in tattoo ink uptake of all blood cells, but also exhibited reduced viability upon incubation with tattoo ink. Interestingly, granulocytes and lymphocytes demonstrated only temporary ink uptake, with flow cytometric signals declining after 24 hours. Mechanistic studies showed that corticosteroids and dexpanthenol did not promote ink excretion from macrophages, but even slightly increased ink retention. The highly motile monocytes, precursors of macrophages, may play an underrated role in the translocation of tattoo ink from dermal blood vessels into internal organs.
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%U https://publications.rwth-aachen.de/record/1012439