Degradable ZnS-Supported Bioorthogonal Nanozymes with Enhanced Catalytic Activity for Intracellular Activation of Therapeutics
Xianzhi Zhang, Shichao Lin, Rui Huang, Aarohi Gupta, Stefano Fedeli, Roberto Cao‐Milán, David C. Luther, Yuanchang Liu, Mingdi Jiang, Gengtan Li, Brayan Rondon, Hui Wei, Vincent M. Rotello
Abstract
Bioorthogonal catalysis using transition-metal catalysts (TMCs) provides a toolkit for the in situ generation of imaging and therapeutic agents in biological environments. Integrating TMCs with nanomaterials mimics key properties of natural enzymes, providing bioorthogonal “nanozymes”. ZnS nanoparticles provide a platform for bioorthogonal nanozymes using ruthenium catalysts embedded in self-assembled monolayers on the particle surface. These nanozymes uncage allylated profluorophores and prodrugs. The ZnS core combines the non-toxicity and degradability with the enhancement of Ru catalysis through the release of thiolate surface ligands that accelerate the rate-determining step in the Ru-mediated deallylation catalytic cycle. The maximum rate of reaction (Vmax) increases ∼2.5-fold as compared to the non-degradable gold nanoparticle analogue. The therapeutic potential of these bioorthogonal nanozymes is demonstrated by activating a chemotherapy drug from an inactive prodrug with efficient killing of cancer cells.