Citation

BibTex format

@article{Chan:2021:10.1039/d1sc02273c,
author = {Chan, TG and Ruehl, CL and Morse, SV and Simon, M and Rakers, V and Watts, H and Aprile, FA and Choi, JJ and Vilar, R},
doi = {10.1039/d1sc02273c},
journal = {Chemical Science},
pages = {9485--9493},
title = {Modulation of amyloid-beta aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound},
url = {http://dx.doi.org/10.1039/d1sc02273c},
volume = {12},
year = {2021}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - One of the key hallmarks of Alzheimer's disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt amyloid-β aggregation. While a handful of molecules have been shown to inhibit amyloid-β aggregation in vitro, there remains a lack of in vivo data reported due to their inability to cross the blood–brain barrier. Here, we investigate a series of new metal complexes for their ability to inhibit amyloid-β aggregation in vitro. We demonstrate that octahedral cobalt complexes with polyaromatic ligands have high inhibitory activity thanks to their dual binding mode involving π–π stacking and metal coordination to amyloid-β (confirmed via a range of spectroscopic and biophysical techniques). In addition to their high activity, these complexes are not cytotoxic to human neuroblastoma cells. Finally, we report for the first time that these metal complexes can be safely delivered across the blood–brain barrier to specific locations in the brains of mice using focused ultrasound.
AU - Chan,TG
AU - Ruehl,CL
AU - Morse,SV
AU - Simon,M
AU - Rakers,V
AU - Watts,H
AU - Aprile,FA
AU - Choi,JJ
AU - Vilar,R
DO - 10.1039/d1sc02273c
EP - 9493
PY - 2021///
SN - 2041-6520
SP - 9485
TI - Modulation of amyloid-beta aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound
T2 - Chemical Science
UR - http://dx.doi.org/10.1039/d1sc02273c
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000664534500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://pubs.rsc.org/en/content/articlelanding/2021/SC/D1SC02273C
UR - http://hdl.handle.net/10044/1/90980
VL - 12
ER -

Contact:

Professor Ramon Vilar
Department of Chemistry
Imperial College London
Molecular Sciences Research Hub
White City Campus
82 Wood Lane
London W12 0BZ
 
Email: r.vilar@imperial.ac.uk
Tel: +44(0)20 7594 1967