Abstract
The facile and modular functionalization of gold nanoparticles makes them versatile tools in nanomedicine, for instance, photothermal therapy, contrast agents or as model nanoparticles to probe drug-delivery mechanisms. Since endothelial cells from various locations in the body exhibit unique phenotypes we quantitatively examined the amount of different sized poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles internalized into primary human dermal endothelial cells or human brain endothelial cells (hCMEC/D3) by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and visualized the nanoparticles using light and electron microscopy. Poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles exhibited high uptake into brain endothelial cells and were used to examine transport mechanisms across the blood-brain barrier using a well-established in vitro model of the blood-brain barrier. Our results demonstrate that 35 nm-sized gold nanoparticles were internalized best into human brain endothelial cells by a flotillin-dependent endocytotic pathway. The uptake into the cells is not correlated with transport across the blood-brain barrier. We demonstrated that the surface modification of gold nanoparticles impacts the internalization process in different cells. In addition, to evaluating toxicity and uptake potential of nanoparticles into cells, the transport properties across cell barriers are important criteria to classify nanoparticle properties regarding targeted delivery of drugs.
Highlights
Specific tumor detection, targeting of pharmacological substances and visualization of specific factors in the body are some challenges which as yet are not adequately resolved
In vitro studies demonstrated that primary human dermal microvascular endothelial cells (HDMEC) preferably internalize 35 nm poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles compared to gold nanoparticles with different neutral-charged polymer shells (i.e. PEG) and different sizes.[10]
Based on the previously published data which demonstrate that the internalization of AuNPs in HDMEC is dependent on the surface modification of the NPs,[10] we determined the uptake of three different-sized poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles (AuNPs) in brain microvascular endothelial cells and compared the results with those obtained for dermal microvascular endothelial cells
Summary
Specific tumor detection, targeting of pharmacological substances and visualization of specific factors in the body are some challenges which as yet are not adequately resolved. This is especially true when the brain is the target for anti-tumor drugs, substrates for imaging and medications against aging diseases. The use of nanoparticles, especially of gold nanoparticles (AuNPs), may be a promising method to solve many problems (similar to CTAB) should be prevented to ensure nanoparticle safety.[9] Besides the exclusion of cytotoxicity caused by. AuNPs, the uptake potential and methods of uptake of specific nanoparticles in different cell types are of great interest.
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