Abstract
Nanotechnology-based drug design offers new possibilities for the use of nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated quantum dots QD655 were studied in human skin MSCs. The effect of QD on MSCs was examined using a cell viability assay, Ki67 expression analysis, and tri-lineage differentiation assay. The optimal conditions for QD uptake in MSCs were determined using flow cytometry. The QD uptake route in MSCs was examined via fluorescence imaging using endocytosis inhibitors for the micropinocytosis, phagocytosis, lipid-raft, clathrin- and caveolin-dependent endocytosis pathways. These data showed that QDs were efficiently accumulated in the cytoplasm of MSCs after incubation for 6 h. The main uptake route of QDs in skin MSCs was clathrin-mediated endocytosis. QDs were mainly localized in early endosomes after 6 h as well as in late endosomes and lysosomes after 24 h. QDs in concentrations ranging from 0.5 to 64 nM had no effect on cell viability and proliferation. The expression of MSC markers, CD73 and CD90, and hematopoietic markers, CD34 and CD45, as well as the ability to differentiate into adipocytes, chondrocytes, and osteocytes, were not altered in the presence of QDs. We observed a decrease in the QD signal from labelled MSCs over time that could partly reflect QD excretion. Altogether, these data suggest that QD-labelled MSCs could be used for targeted drug delivery studies.
Highlights
Despite remarkable advances in targeted therapies of various human malignancies, cancer is one of the leading causes of death worldwide [1]
The concentration-dependent cytotoxicity of quantum dots (QDs) was analysed in mesenchymal stem cells (MSCs) cultures after 24 and 48 h using a colorimetric Cell Counting Kit 8 (CCK-8) assay, which measures intracellular dehydrogenase activity (Figure 1)
In order to select the optimal incubation time for QD uptake in skin MSCs, cells were incubated with 16 nM QDs for time periods ranging from 15 min to 48 h (Figure 2a)
Summary
Despite remarkable advances in targeted therapies of various human malignancies, cancer is one of the leading causes of death worldwide [1]. Nanoparticles (NPs) could be linked to various drugs, thereby making them suitable for tumour imaging and targeted therapy [2]. The fact that NPs are quickly recognised by immune cells and cleared from the blood stream by reticuloendothelial system limits their utility as drug carriers [3]. Recent studies have shown that nano-engineered mesenchymal stem cells (MSCs) could be used as tumour-targeted therapeutic carriers, reflecting their tumourhoming capabilities [4,5,6]. MSCs are present in many tissues of the human body, including bone marrow, adipose tissues, skin and dental pulp. Other cell types, such as neurons, glial cells and smooth muscle cells, could be obtained from MSCs under the appropriate cell culture conditions [9,10]
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