Angiopoietin-1 Mimetic Nanoparticles for Restoring the Function of Endothelial Cells as Potential Therapeutic for Glaucoma.

Angpt-1 mimetic POAG Schlemm’s canal Tie2 angiopoietin 1 eNOS glaucoma nanoparticles peptide

Journal

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453

Informations de publication

Date de publication:
24 Dec 2021
Historique:
received: 25 11 2021
revised: 16 12 2021
accepted: 21 12 2021
entrez: 21 1 2022
pubmed: 22 1 2022
medline: 22 1 2022
Statut: epublish

Résumé

A root cause for the development and progression of primary open-angle glaucoma might be the loss of the Schlemm's canal (SC) cell function due to an impaired Angiopoietin-1 (Angpt-1)/Tie2 signaling. Current therapeutic options fail to restore the SC cell function. We propose Angpt-1 mimetic nanoparticles (NPs) that are intended to bind in a multivalent manner to the Tie2 receptor for successful receptor activation. To this end, an Angpt-1 mimetic peptide was coupled to a poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) block co-polymer. The modified polymer allowed for the fabrication of Angpt-1 mimetic NPs with a narrow size distribution (polydispersity index < 0.2) and the size of the NPs ranging from about 120 nm (100% ligand density) to about 100 nm (5% ligand density). NP interaction with endothelial cells (HUVECs, EA.hy926) as surrogate for SC cells and fibroblasts as control was investigated by flow cytometry and confocal microscopy. The NP-cell interaction strongly depended on the ligand density and size of NPs. The cellular response to the NPs was investigated by a Ca

Identifiants

pubmed: 35056075
pii: ph15010018
doi: 10.3390/ph15010018
pmc: PMC8780450
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : BR3566/3-3
Organisme : Deutsche Forschungsgemeinschaft
ID : FU734/4-3

Références

Angew Chem Int Ed Engl. 2014 May 12;53(20):5093-6
pubmed: 24700480
Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):803-814
pubmed: 29392327
Blood. 2008 Apr 15;111(8):4145-54
pubmed: 18252863
Nat Rev Dis Primers. 2016 Sep 22;2:16067
pubmed: 27654570
Invest Ophthalmol Vis Sci. 2011 Dec 09;52(13):9438-44
pubmed: 22039240
J Control Release. 2013 Apr 10;167(1):76-84
pubmed: 23369761
J Ocul Biol. 2013 Jun;1(1):3
pubmed: 24364042
Mol Cell. 2010 Mar 12;37(5):643-55
pubmed: 20227369
Int J Nanomedicine. 2010 Nov 26;5:1057-65
pubmed: 21170353
ACS Appl Mater Interfaces. 2020 Aug 5;12(31):34689-34702
pubmed: 32639709
Am J Physiol Lung Cell Mol Physiol. 2011 Jun;300(6):L851-62
pubmed: 21421750
Pharmaceutics. 2020 Jul 27;12(8):
pubmed: 32727014
J Clin Invest. 2017 Oct 2;127(10):3594-3597
pubmed: 28920923
Exp Eye Res. 2008 Apr;86(4):543-61
pubmed: 18313051
Macromol Biosci. 2020 Apr;20(4):e1900427
pubmed: 32077622
Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4376-4381
pubmed: 28396439
J Cell Biol. 2005 Apr 25;169(2):239-43
pubmed: 15851516
Biomed Res Int. 2015;2015:141905
pubmed: 26557650
ACS Appl Mater Interfaces. 2015 May 20;7(19):10374-85
pubmed: 25909493
Am J Hosp Pharm. 1985 Jul;42(7):1568-71
pubmed: 4025356
Invest Ophthalmol Vis Sci. 2014 Nov 13;55(12):8067-76
pubmed: 25395486
Cytokine Growth Factor Rev. 2013 Dec;24(6):579-92
pubmed: 23838360
J Exp Pharmacol. 2021 Feb 25;13:197-212
pubmed: 33664600
J Drug Deliv. 2013;2013:374252
pubmed: 23533769
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5547-52
pubmed: 15060279
Expert Opin Ther Targets. 2017 Nov;21(11):1037-1050
pubmed: 28952395
Nanotechnology. 2020 Mar 27;31(13):132002
pubmed: 31770746
Polymers (Basel). 2011 Sep 1;3(3):1377-1397
pubmed: 22577513
Am J Pathol. 2003 Jun;162(6):1927-36
pubmed: 12759249
Invest Ophthalmol Vis Sci. 2016 Feb;57(2):692-706
pubmed: 26903228
J Sex Med. 2013 Dec;10(12):2912-27
pubmed: 23937122
Nat Commun. 2017 Jul 18;8:16106
pubmed: 28719590
Trends Mol Med. 2013 Jan;19(1):31-9
pubmed: 23182855
J Clin Invest. 2017 Oct 2;127(10):3877-3896
pubmed: 28920924
Invest Ophthalmol Vis Sci. 2007 Feb;48(2):715-26
pubmed: 17251470
Nanoscale. 2017 Apr 6;9(14):4787-4792
pubmed: 28345718
Drug Discov Today. 2019 Aug;24(8):1606-1613
pubmed: 30905679
ACS Appl Mater Interfaces. 2019 Jan 9;11(1):1311-1320
pubmed: 30521749
Circ Res. 2005 Jun 24;96(12):1282-90
pubmed: 15920022
Exp Eye Res. 1989 Jan;48(1):117-30
pubmed: 2920779
EMBO Rep. 2004 Mar;5(3):262-7
pubmed: 14978510
Prog Retin Eye Res. 2021 Jul;83:100922
pubmed: 33253900
Transl Vis Sci Technol. 2020 Mar 18;9(4):16
pubmed: 32818103
J Funct Biomater. 2015 Sep 21;6(3):963-85
pubmed: 26402712
Tissue Eng Part A. 2009 Jun;15(6):1269-80
pubmed: 18939935
Biol Direct. 2016 Oct 21;11(1):55
pubmed: 27769290
Prog Retin Eye Res. 2015 Jan;44:86-98
pubmed: 25223880

Auteurs

Raphael Mietzner (R)

Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Ramona Pawlak (R)

Department of Human Anatomy and Embryology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Ernst R Tamm (ER)

Department of Human Anatomy and Embryology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Achim Goepferich (A)

Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Rudolf Fuchshofer (R)

Department of Human Anatomy and Embryology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Miriam Breunig (M)

Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.

Classifications MeSH