Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics
Dr. M. Carmen Ortega-Liebana
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Nicola J. Porter
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Catherine Adam
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorDr. Teresa Valero
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorDr. Lloyd Hamilton
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Search for more papers by this authorDr. Dirk Sieger
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Search for more papers by this authorProf. Catherina G. Becker
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany
Search for more papers by this authorCorresponding Author
Prof. Asier Unciti-Broceta
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorDr. M. Carmen Ortega-Liebana
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Nicola J. Porter
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Catherine Adam
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorDr. Teresa Valero
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorDr. Lloyd Hamilton
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Search for more papers by this authorDr. Dirk Sieger
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Search for more papers by this authorProf. Catherina G. Becker
Centre for Discovery Brain Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh, EH16 4SB UK
Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany
Search for more papers by this authorCorresponding Author
Prof. Asier Unciti-Broceta
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU UK
Search for more papers by this authorGraphical Abstract
Making drugs in the brain! Fully-biocompatible Au catalysis enables for the first time the localized uncaging of a neuroactive agent, the anxiolytic drug fluoxetine, directly in the head of zebrafish by using catalytically-enhanced Au-polymer composites as safe catalytic reactors.
Abstract
Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled -for the first time- modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal.
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