Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts
Xianzhi Zhang, Ryan F. Landis, Puspam Keshri, Roberto Cao‐Milán, David C. Luther, S. Gopalakrishnan, Yuanchang Liu, Rui Huang, Gengtan Li, Morgane Malassiné, Imad Uddin, Brayan Rondon, Vincent M. Rotello
Abstract
Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro-dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal "polyzymes," is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media. The therapeutic potential of these polyzymes is demonstrated by the transformation of a nontoxic prodrug to an anticancer drug (mitoxantrone), leading to the cancer cell death in vitro.