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Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy

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Title: Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy
Authors: Mohamed, NA
Davies, RP
Lickiss, PD
Ahmetaj-Shala, B
Reed, DM
Gashaw, HH
Saleem, H
Freeman, GR
George, PM
Wort, SJ
Morales-Cano, D
Barreira, B
Tetley, TD
Chester, AH
Yacoub, MH
Kirkby, NS
Moreno, L
Mitchell, JA
Item Type: Journal Article
Abstract: Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.
Issue Date: 27-Jun-2017
Date of Acceptance: 12-Apr-2017
URI: http://hdl.handle.net/10044/1/48110
DOI: https://dx.doi.org/10.1177/2045893217710224
ISSN: 2045-8940
Publisher: University of Chicago Press
Start Page: 1
End Page: 11
Journal / Book Title: Pulmonary Circulation
Volume: 7
Issue: 3
Copyright Statement: © 2017 by Pulmonary Vascular Research Institute.This article is distributed under the terms of the Creative Commons Attribution 4.0 License http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and dis- tribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Sponsor/Funder: Wellcome Trust
Pulmonary Hypertension Association UK
Medical Research Council
Qatar Foundation
Funder's Grant Number: 085255/Z/08/Z
Keywords: MIL-89
endothelial cells
vascular smooth muscle cells
Publication Status: Published
Appears in Collections:Chemistry
National Heart and Lung Institute
Faculty of Natural Sciences