Uptake of poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles in microvascular endothelial cells and transport across the blood–brain barrier

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. † Electronic supplementary information (ESI) available: Detailed information about the cell viability after gold nanoparticle treatment, the microscopic analysis of the internalization process after 4 hours within HDMEC and hCMEC/D3 and the co-localization with flotillin-1-positive vesicles is available online. See

The influence of flow, shear stress and adhesion molecule targeting on gold nanoparticle uptake in human endothelial cells

“…32 Furthermore, microarray analysis of HUVECs showed regulation of 52 genes after 6 h and 24 h of shear stress adaptation (25 dyn), among these down-regulations of caveolin-1 and α-tubulin (subunits of microtubules). 36 The integrity of both clathrin-and flotillin-dependent endocytotic pathways has also been associated with F-actin and dynamic changes of the actin cytoskeleton. 7 This includes the expressional downregulation of coronin-1A (coronin-like protein p57), which has been suggested to be directly involved in phagocytosis via interaction with Arp2/3 and F-actin in human neutrophils and in mouse RAW 264.7 macrophages.…”

“…This is to our knowledge the first time that targeted metallic NPs have been used in this context, whereas targeting of activated endothelial cells with anti-ICAM-1 polystyrene NPs has been studied for various sizes (0.18-10 µm) and shapes in HUVECs and an endothelial-like cell line, EAhy926. 27,35,36 ICAM-1 conjugated NPs have in turn been suggested to be internalised by a clathrin-and caveolae-independent pathway, described as CAM-mediated endocytosis, which requires the clustering of ICAM-1 receptors. 14,16,40 The pronounced increase of Au 1 2 Ab internalisation in TNF-activated HUVECs can be explained by differences in the internalisation pathways of Au 1 2 Ab and AuCtrl.…”

Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues

“…We have previously shown that glucose-coated gold nanoparticles (covalently bound glucose with a C2-linker) are transported across endothelium from brain, aorta or bone marrow at different rates [17]. Similarly, other studies have noted different rates of uptake by endothelia of different origin or epithelia [18–20]. Yet investigations to explain this phenomenon are lacking even though they may help to achieve tissue-selective targeting of nanoparticles.…”

Synthesis and characterisation of morin reduced gold nanoparticles and its cytotoxicity in MCF-7 cells

“…53 Hence development of biocompatible AuNPs synthesised using 54 phytochemicals with appropriate reactive groups which are toxic 55 to cancer cells hold great potential in nanomedicine [9,10]. 56 A possible application of these AuNPs is in the treatment of 57 breast cancer. The incidence of breast cancer has increased in Asian 58 countries in the past few decades with over 90,000 cases diagnosed 59 annually in India [11,12], a large portion of which being hormone 60 dependent [13].…”