Abstract
The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo. Nanoparticle uptake and subcellular localisation was quantified by transmission electron microscopy. The rate of internalisation was approximately 4x higher in kidney endothelium than brain endothelium. Vesicular endocytosis was approximately 4x greater than cytosolic uptake in both cell types, and endocytosis was blocked by metabolic inhibition, whereas cytosolic uptake was energy-independent. The cellular basis for the different rates of internalisation was investigated. Morphologically, both endothelia had similar profiles of vesicles and cell volumes. However, the rate of endocytosis was higher in kidney endothelium. Moreover, the glycocalyces of the endothelia differed, as determined by lectin-binding, and partial removal of the glycocalyx reduced nanoparticle uptake by kidney endothelium, but not brain endothelium. This study identifies tissue-specific properties of vascular endothelium that affects their interaction with nanoparticles and rate of transport.
Highlights
Nanoparticles hold great potential in biomedicine; for diagnosis or as carriers of therapeutic agents to different tissues
We have demonstrated that glucose-coated gold nanoparticles cross human brain endothelium in vitro and they can rapidly enter the brain of rats in vivo, following intra-vascular injection [17,26]
To explain the higher uptake of the nanoparticles by kidney endothelium we considered 3 possible mechanisms: (a) the surface properties of the endothelium are different so that the initial binding of the nanoparticles to the cells varies; (b) the rate of endocytosis is comparatively low in the brain endothelium; (c) morphological features of the cell lines, such as vesicle numbers or size of the cells may differ between the endothelia
Summary
Nanoparticles hold great potential in biomedicine; for diagnosis or as carriers of therapeutic agents to different tissues. A central problem is how the nanoparticles can be selectively delivered to the target tissue. Nanoparticles in the blood stream first interact with vascular endothelium before they may cross or pass the endothelial cells and enter the tissue. Vascular endothelium in different tissues has distinctive properties including its glycocalyx, surface receptors, intercellular junctions or rate of production of transport vesicles. These distinctive properties provide an opportunity to selectively target nanoparticles.
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