Abstract
In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.
Highlights
To advance the field of nanomedicine, innovative nanoparticle formulations with suitable properties for diagnostic imaging, therapy, delivery of drugs and siRNA have been developed
1) In general, an elongated shape of gold nanoparticle rods and gold@metal oxide Janus particles leads to a stronger reduction in cell metabolic activity
2) Endothelial cells react sensitively towards positively charged surfaces, e.g., caused by the surfactants NH2 and CyA. 3) Internalization of nanoparticles is driven by a positive surface and a small nanoparticle size
Summary
To advance the field of nanomedicine, innovative nanoparticle formulations with suitable properties for diagnostic imaging, therapy (e.g., magnetic hyperthermia), delivery of drugs and siRNA have been developed. We 1) analyzed the behavior of spherical metal oxide nanoparticles in comparison to asymmetric elongated gold@metal oxide nanoparticles, 2) determined the impact of different nanoparticle materials on cell life, 3) investigated the effects of the surface coating and the surface charge of QDs (cationic, anionic, or neutral) on cell metabolism, membrane integrity and uptake, 4) monitored the cellular localization depending on the size and shape of different nanoparticles and 5) investigated endocytotic pathways of nanoparticles to gather insights into their uptake mechanisms.
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