Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMC) offers a promising strategy for imaging and therapeutic applications. However, maintaining activity and controlling the localization of TMCs make their use in biomedical applications challenging. Here we report the engineering of nanoparticles of gold nanoparticles (AuNPs) with encapsulated TMCs (nanozymes) to provide specific intra- and extracellular localization. We used membrane-penetrating cationic nanoparticles for catalysis inside and ‘stealth’ zwitterionic particles to limit catalysis to outside of mammalian cells. Specific localization of nanozyme activity was demonstrated through profluorophore activation. Therapeutic efficacy was demonstrated through intra- and extracellular activation of a prodrug. The ability to control nanozyme localization was further shown by targeting biofilms in a complex bio-system using a co-culture model. We designed pH-switchable nanozymes that effectively localize in the acidic microenvironment of biofilms. These nanozymes generate imaging agents through bioorthogonal activation of profluorophores inside biofilms demonstrating potential for early detection of biofilm-associated infections. Taken together, these studies demonstrate a new level of spatial control for TMC-mediated bioorthogonal catalysis for diagnostic and therapeutic purposes.

Engineered nanozymes to catalyze site-specific bioorthogonal reactions for imaging and therapeutic applications

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.