Controlled and Selective Photo-oxidation of Amyloid-β Fibrils by Oligomeric p -Phenylene Ethynylenes.

Autor:	Fanni AM; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Biomedical Engineering Graduate Program, University of New Mexico, Albuquerque, New Mexico 87131, United States., Okoye D; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States., Monge FA; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Biomedical Engineering Graduate Program, University of New Mexico, Albuquerque, New Mexico 87131, United States., Hammond J; Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Rose-Hulman Institute of Technology, Terre Haute, Indiana 47803, United States., Maghsoodi F; Nanoscience and Microsystems Engineering Graduate Program, University of New Mexico, Albuquerque, New Mexico 87131, United States., Martin TD; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Biomedical Engineering Graduate Program, University of New Mexico, Albuquerque, New Mexico 87131, United States., Brinkley G; Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Chemical Engineering Department, University of Minnesota, Duluth, Minnesota 55812, United States., Phipps ML; Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States., Evans DG; Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, United States., Martinez JS; Center for Materials Interfaces in Research and Applications, Northern Arizona University, Flagstaff, Arizona 86011, United States.; Department of Applied Physics and Materials Science, Northern Arizona University, Flagstaff, Arizona 86011, United States., Whitten DG; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States., Chi EY; Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.; Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.
Jazyk:	angličtina
Zdroj:	ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2022 Apr 06; Vol. 14 (13), pp. 14871-14886. Date of Electronic Publication: 2022 Mar 28.
DOI:	10.1021/acsami.1c22869
Abstrakt:	Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer's disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo- p -phenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-β (Aβ) and α-synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aβ fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aβ40, OPE oxidized only Aβ40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic β-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE's photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.
Databáze:	MEDLINE
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