Bioorthogonal activation of prodrugs provides a strategy for on-demand production of therapeutics. Intracellular activation provides a strategy to localize therapeutics, potentially minimizing off-target effects. In this study nanoparticles embedded with transition metal catalysts (nanozymes) were engineered to generate either ‘hard’ irreversible or ‘soft’ reversible coronas in serum. The hard corona effectively inhibited nanozyme activity, whereas only partial loss of activity was observed with the soft corona nanozymes. In both cases, complete activity was restored by treatment with protease. Intracellular activity mirrored this reactivation: endogenous proteases in the endosome provided intracellular activation of both nanozymes. The role of intracellular proteases in nanozyme reactivation was verified through the treatment of the cells with protease inhibitors, which prevented reactivation. Taken together, this study demonstrates the use of intracellular proteolysis as a strategy for the localization of therapeutic generation within cells.

Intracellular activation of bioorthogonal nanozymes through endosomal proteolysis of the protein corona

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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