Abstract
Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene) (PMAOD). The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications.
Highlights
The superior optical properties of quantum dots (QD) compared to organic dyes render them promising candidates for the demands of sophisticated in vivo imaging in biomedical diagnosis [1]
In order to investigate potential pro-inflammatory pathways of injected nanocrystals and to study their hepatocellular route, we recently established the methodology for the embedding of QDs, superparamagnetic iron oxide nanocrystals (SPIO) and 59Fe-SPIOs either by an amphiphilic polymer coat [21] or by the incorporation into the lipid core of micelles [17,18], as indicated in the schematic model (Figure 1A)
The liver rapidly clears polymer-coated 59Fe-SPIOs [19], the exact molecular mechanisms and cell types involved in the processing of these particles are not clarified in detail
Summary
The superior optical properties of QDs compared to organic dyes render them promising candidates for the demands of sophisticated in vivo imaging in biomedical diagnosis [1]. The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals.
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