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Mohamed NA, Davies RP, Lickiss PD, et al. 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. Pulm Circ. 2017;7(3):643-653doi: 10.1177/2045893217710224.
Mohamed, N. A., Davies, R. P., Lickiss, P. D., Ahmetaj-Shala, B., Reed, D. M., Gashaw, H. H., Saleem, H., Freeman, G. R., George, P. M., Wort, S. J., Morales-Cano, D., Barreira, B., Tetley, T. D., Chester, A. H., Yacoub, M. H., Kirkby, N. S., Moreno, L., & Mitchell, J. A. (2017). 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. Pulmonary circulation, 7(3), 643-653. https://doi.org/10.1177/2045893217710224
Mohamed, Nura A, et al. "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." Pulmonary circulation vol. 7,3 (2017): 643-653. doi: https://doi.org/10.1177/2045893217710224
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. 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. Pulm Circ. 2017 Jul-Sep;7(3):643-653. doi: 10.1177/2045893217710224. Epub 2017 Jun 27. PMID: 28447910; PMCID: PMC5841901.
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Pulm Circ. 2017 Jul-Sep;7(3):643-653. doi: 10.1177/2045893217710224. Epub 2017 Jun 27.

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.

Pulmonary circulation

Nura A Mohamed, Robert P Davies, Paul D Lickiss, Blerina Ahmetaj-Shala, Daniel M Reed, Hime H Gashaw, Hira Saleem, Gemma R Freeman, Peter M George, Stephen J Wort, Daniel Morales-Cano, Bianca Barreira, Teresa D Tetley, Adrian H Chester, Magdi H Yacoub, Nicholas S Kirkby, Laura Moreno, Jane A Mitchell

Affiliations

  1. 1 Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London, UK.
  2. 2 Heart Science Centre at Harefield Hospital, Harefield, UK.
  3. 3 Qatar Foundation Research and Development Division, Doha, Qatar.
  4. 4 Department of Chemistry, South Kensington Campus, Imperial College, London, UK.
  5. 5 Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid- Instituto de Investigacion Sanitaria Gregorio Marañón (IiSGM), Ciber Enfermedades Respiratorias (CIBERES), Spain.
  6. 6 Lung Cell Biology Group, National Heart and Lung Institute, Imperial College London, London, UK.

PMID: 28447910 PMCID: PMC5841901 DOI: 10.1177/2045893217710224

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.

Keywords: MIL-89; MIL-89 PEG; endothelial cells; nanoparticles; nanotechnology; vascular smooth muscle cells

References

  1. Curr Opin Chem Biol. 2010 Apr;14(2):262-8 - PubMed
  2. Dalton Trans. 2008 Oct 28;(40):5462-4 - PubMed
  3. Int J Pharm. 2016 Sep 25;511(2):1042-7 - PubMed
  4. Circ Res. 2014 Feb 14;114(4):677-88 - PubMed
  5. Br J Pharmacol. 1998 Nov;125(5):1102-8 - PubMed
  6. FASEB J. 2015 Jun;29(6):2595-602 - PubMed
  7. Clin Chest Med. 2001 Sep;22(3):529-37, x - PubMed
  8. Acc Chem Res. 2011 Oct 18;44(10):957-68 - PubMed
  9. Expert Opin Drug Deliv. 2015 Feb;12(2):239-61 - PubMed
  10. N Engl J Med. 1992 Jul 9;327(2):70-5 - PubMed
  11. Nat Protoc. 2012 Sep;7(9):1709-15 - PubMed
  12. Curr Opin Biotechnol. 2003 Jun;14(3):337-46 - PubMed
  13. Am J Cardiol. 2013 Mar 4;111(5 Suppl):1A-16A; quiz 17A-19A - PubMed
  14. Circulation. 2014 May 27;129(21):2125-35 - PubMed
  15. Nat Mater. 2010 Feb;9(2):172-8 - PubMed
  16. N Engl J Med. 1993 Jun 17;328(24):1732-9 - PubMed
  17. Methods Enzymol. 2012;508:325-54 - PubMed
  18. Nat Methods. 2012 Jul;9(7):671-5 - PubMed
  19. Angew Chem Int Ed Engl. 2004 Nov 26;43(46):6285-9 - PubMed
  20. Br J Pharmacol. 1994 Nov;113(3):1008-14 - PubMed
  21. Blood. 2013 Apr 4;121(14):2773-84 - PubMed
  22. Blood. 2011 Jan 20;117(3):1071-80 - PubMed
  23. Br J Pharmacol. 2010 Aug;160(8):1997-2007 - PubMed
  24. Glob Cardiol Sci Pract. 2014 Dec 31;2014(4):382-93 - PubMed
  25. Chem Commun (Camb). 2006 Apr 14;(14):1518-20 - PubMed
  26. Exp Physiol. 2012 May;97(5):676-86 - PubMed
  27. J Heart Lung Transplant. 2015 Nov;34(11):1366-75 - PubMed
  28. Circ Cardiovasc Imaging. 2014 Mar;7(2):303-11 - PubMed
  29. Science. 2005 Sep 23;309(5743):2040-2 - PubMed
  30. Circulation. 2010 May 11;121(18):2045-66 - PubMed
  31. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7 - PubMed
  32. PLoS One. 2012;7(8):e42386 - PubMed
  33. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D34-41 - PubMed
  34. Circulation. 2003 Jul 1;107(25):3230-5 - PubMed
  35. Orphanet J Rare Dis. 2013 Jul 06;8:97 - PubMed
  36. Prog Cardiovasc Dis. 2002 Nov-Dec;45(3):173-202 - PubMed
  37. Angew Chem Int Ed Engl. 2006 Sep 11;45(36):5974-8 - PubMed
  38. Glob Cardiol Sci Pract. 2013 Nov 01;2013(1):37-43 - PubMed
  39. Circulation. 2004 Jan 20;109(2):159-65 - PubMed
  40. J Cardiovasc Transl Res. 2016 Apr;9(2):162-4 - PubMed
  41. Mayo Clin Proc. 2009 Feb;84(2):191-207 - PubMed
  42. Blood. 2004 Nov 1;104(9):2752-60 - PubMed
  43. Am J Pathol. 2014 Feb;184(2):369-75 - PubMed
  44. Adv Drug Deliv Rev. 2001 Dec 3;53(1):95-108 - PubMed

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