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@PHDTHESIS{Lin:1012439,
author = {Lin, Cheng},
othercontributors = {Bartneck, Matthias and Röth, Anjali},
title = {{E}xploring the interaction of lipid nanoparticles and
tattoo pigments with macrophages},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2025-04992},
pages = {39, 19 Seiten : Illustrationen},
year = {2025},
note = {Dissertation, Rheinisch-Westfälische Technische Hochschule
Aachen, 2025, Kumulative Dissertation},
abstract = {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.},
cin = {531030-2 ; 932710},
ddc = {610},
cid = {$I:(DE-82)531030-2_20140620$},
typ = {PUB:(DE-HGF)11},
url = {https://publications.rwth-aachen.de/record/1012439},
}
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