Methods based on nanotechnologies play a growing role in biomedical research. Quantum
dots (QDs) are a group of engineered fluorescent nanoparticles suited for advanced
imaging applications. The substitution of the particle’s surface with defined molecular
structures could enable the adoption as targeted contrast agents or therapeutic devices for
a variety of clinical approaches. However, important aspects such as the basic surfacedependent
behavior of non-targeted QDs in the organism and arising health effects upon
systemic administration remain incompletely understood. Acute inflammatory effects for
instance are often initiated on the microcirculatory level and are probably relevant for
cardiovascular pathologies observed in epidemiologic and experimental studies of certain
nanoparticles. Most in vitro studies show that the surface structures of QDs and other
nanoparticles seem to be predominantly accountable for different cytotoxic effects and a
variable potential to liberate proinflammatory cytokines. Currently, no systematic in vivo
studies have addressed surface-dependent interactions of QDs on the level of the
microcirculation and assessed the resulting impact on biokinetics as well as on
proinflammatory parameters. Thus, this thesis aimed to i) analyze the incidence of QDsurface-
dependent acute microvascular interactions and their influence on key biokinetic
parameters and ii) investigate acute immunomodulatory effects on the multistep process
of leukocyte recruitment in vivo. For this, three types of commercially available QDs with
different surface modifications: carboxyl-QDs, amine- and polyethylene glycol-QDs
(amine-QDs) and polyethylene glycol-QDs (PEG-QDs) were used. The physicochemical
characterization was done by dynamic light scattering (DLS) analysis and microscale
thermophoresis. In a first set of experiments, circulating half-lives, tissue distribution in
different organs, and hepatic as well as renal clearance were measured. Ex vivo analysis
of QD tissue distribution was performed on selected tissue samples via transmission
electron microscopy (TEM) and two-photon microscopy. By combining reflected-light
oblique transillumination (RLOT) and fluorescence in vivo microscopy of the murine M.
cremaster, interactions of QDs with components of the microcirculation as well as
leukocyte migration parameters were visualized and quantified. The extreme short
circulating half-life of anionic carboxyl-QDs was related to pronounced clearance by the
mononuclear phagocyte system. Beyond this, further investigations showed, for the first
time, that the continuous capillary endothelium of skeletal and heart muscle tissue has the
capacity to directly extract carboxyl-QDs from the circulation by means of caveolaemediated
endocytosis. Carboxyl-QDs were also taken up by perivascular macrophages in
the surgically exposed but not in the native M. cremaster and led to a significant increase
of adherent and (subsequently) transmigrated leukocytes in this model. Further
experiments provided evidence for a probable involvement of mast cells in the
intercellular adhesion molecule-1 (ICAM-1)- and endothelial (E)-selectinmediated
modulation of leukocyte recruitment. This process is most likely initiated by the
endocytosis of carboxyl-QDs through activated perivascular macrophages. The primary
activation of tissue-resident perivascular macrophages seems to be the consequence of
tissue damage related to the surgical preparation of the cremaster muscle. This is
supposedly a prerequisite for the endocytosis of carboxyl-QDs whereupon endothelial and
mast cells seem to be secondarily activated in a paracrine fashion that then leads to an
increase in leukocyte recruitment