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.
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.
Keywords: behavioral activity; bioorthogonal; catalysis; gold; prodrug.
© 2021 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.