Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation

Transition-metal catalysts (TMCs) effect bioorthogonal transformations that enable the generation of therapeutic agents in situ, minimizing off-target effects. The encapsulation of insoluble TMCs into polymeric nanoparticles to generate "polyzymes" has vastly expanded their applicability in biological environments by enhancing catalyst solubility and stability. However, commonly used precipitation approaches provide limited encapsulation efficiency in polyzyme fabrication and result in a low catalytic activity. Herein, we report the creation of polyzymes with increased catalyst loading and optimized turnover efficiency using flash nanoprecipitation (FNP). Polyzymes with controlled size and catalyst loading were fabricated by tuning the process conditions of FNP. The biological applicability of polyzymes was demonstrated by efficiently transforming a non-toxic prodrug into the active drug within cancer cells. © 2022 American Chemical Society. All rights reserved.