Controlled bioorthogonal catalyst self-assembly and activity using rationally designed polymer scaffolds

Polymer-based nanocatalysts have been extensively utilized in advanced drug delivery due to their versatility and high reactivity. Incorporating bioorthogonal transition metal catalysts (TMCs) into polymers generates bioorthogonal nanocatalysts capable of producing therapeutic agents <i>in situ</i>, minimizing off-target effects. The supramolecular interactions within the polymer matrix, including hydrophobic interactions and aromatic stacking, play a crucial role in catalytic properties. Our study focuses on co-engineering the host polymer structure and the catalyst encapsulation process to achieve precise control over the supramolecular interactions within the nanoenvironment. By carefully engineering these interactions, we successfully generate thermo-responsive nanocatalysts with a resolution of 6 °C. These nanocatalysts demonstrate thermal activation of the catalytic deprotection of a pro-antibiotic, with concomitant external control of bacterial biofilm eradication.