Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues

Gromnicova, Radka; Kaya, Mehmet; Romero, Ignacio A.; Williams, Phil; Satchell, Simon; Sharrack, Basil and Male, David (2016). Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues. PLoS ONE, 11(8), article no. e0161610.

DOI: https://doi.org/10.1371/journal.pone.0161610

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

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About

• Item ORO ID
• 47164
• Item Type
• Journal Item
• ISSN
• 1932-6203
• Project Funding Details

• Funded Project Name	Project ID	Funding Body
  Targeted delivery of therapeutic transgenes to cells of the human CNS by nanoparticle carriers	SB-13-063-DM	Sheffield Teaching Hospitals
  Role of microRNAs in ageing at the blood-brain barrier: integrated studies in human and mouse models (SB-11-075-IR)	BB/K009184/1	BBSRC (Biotechnology and Biological Sciences Research Council)

• Keywords
• Gold nanoparticles; Blood brain barrier; endothelium; nanocarriers; gene therapy; transcytosis
• Academic Unit or School
• Faculty of Science, Technology, Engineering and Mathematics (STEM)
  Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
• Research Group
• Innovation, Knowledge & Development research centre (IKD)
• Copyright Holders
• © 2016 The Authors
• Depositing User
• David Male