No abstract

Bioorthogonal catalysis offers a unique strategy to modulate biological processes through the in situ generation of therapeutic agents. However, the direct application of bioorthogonal transition metal catalysts (TMCs) in complex media poses numerous challenges due to issues of limited biocompatibility, poor water solubility, and catalyst deactivation in biological environments. We report here the creation of catalytic "polyzymes", comprised of self-assembled polymer nanoparticles engineered to encapsulate lipophilic TMCs. The incorporation of catalysts into these nanoparticle scaffolds creates water-soluble constructs that provide a protective environment for the catalyst. The potential therapeutic utility of these nanozymes was demonstrated through antimicrobial studies in which a cationic nanozyme was able to penetrate into biofilms and eradicate embedded bacteria through the bioorthogonal activation of a proantibiotic.

This paper describes the fabrication of thermoresponsive bio-orthogonal catalytic systems though the integration of transition metal catalysts into gold nanoparticles. The confined assemblies of the catalysts provide a temperatureregulated system able to controllably activate antibiotics within biofilms. This work presents a blueprint for synthesizing a family of reversible thermoresponsive nanozymes with tailored activation temperatures and preserved bio-orthogonal activity in complex biological environments.

Infections caused by bacterial biofilms are challenging to diagnose due to the complexity of both the bacteria and the heterogeneous biofilm matrix. We report here a robust polymer-based sensor array that uses selective interactions between polymer sensor elements and the biofilm matrix to identify bacteria species. In this array, appropriate choice of fluorophore enabled excimer formation and inter-polymer FRET, generating six output channels from three polymers. Selective multivalent interactions of these polymers with the biofilm matrices caused differential changes in fluorescent patterns, providing a species-based signature of the biofilm. The real-world potential of the platform was further validated through identification of mixed-species bacterial biofilms and discrimination of biofilms in a mammalian cell-biofilm co-culture wound model.