title: Microcapsules functionalized with neuraminidase can enter vascular endothelial cells in vitro.
abstract: Microcapsules made of polyelectrolyte multilayers exhibit no or low toxicity, appropriate mechanical stability, variable controllable degradation and can incorporate remote release mechanisms triggered by various stimuli, making them well suited for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. polystyrenesulfonate sodium salt/polyallylamine hydrochloride) or natural (i.e. dextran sulfate/poly-L-arginine) polyelectrolyte and human umbilical vein endothelial cells with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by endothelial cells. Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional confocal images reveal that microcapsules, functionalized with neuraminidase, can be internalized by endothelial cells. Capsules without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 h. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5; however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelial barrier to cross-membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by localized cleavage of glycocalyx components with minimum disruption of the glycocalyx layer and therefore have high potential to act as drug delivery vehicles to reach tissues beyond the endothelial barrier of blood vessels.
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK.
authors.forename: Ke
authors.initials: K
authors.lastname: Bai
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK.
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK g.sukhorukov@qmul.ac.uk.
authors.forename: Gleb
authors.initials: G
authors.lastname: Sukhorukov
authors.affiliation: Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK wen.wang@qmul.ac.uk.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002214:Capsules; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003016:Clostridium perfringens / Q000201:enzymology*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009439:Neuraminidase / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D055672:Static Electricity
chemical_list: D001426:Bacterial Proteins; D002214:Capsules; D004337:Drug Carriers; D009439:Neuraminidase
keywords: biodegradable microcapsules; endothelial glycocalyx; neuraminidase; targeted drug delivery; transport across cell membrane