Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics

Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202111461. doi: 10.1002/anie.202111461. Epub 2021 Nov 18.

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.

Keywords: behavioral activity; bioorthogonal; catalysis; gold; prodrug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / metabolism*
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism*
  • Catalysis
  • Central Nervous System / chemistry
  • Central Nervous System / metabolism*
  • Gold / chemistry
  • Gold / metabolism*
  • Molecular Structure
  • Particle Size
  • Zebrafish

Substances

  • Anti-Anxiety Agents
  • Biocompatible Materials
  • Gold