The encapsulation of bioorthogonal catalysts into polymeric nanoscaffolds yields bioorthogonal nanozymes with properties similar to native enzymes. The nanozyme interior is governed by hydrophobic interactions. In this study, we have modulated nanozyme activity by changing the molecular structure of the bioorthogonal catalyst, leading to substantial differences in assembly and catalytic performance.

Abstract

Bioorthogonal catalysts can mediate uncaging reactions of caged therapeutics in situ, enabling localized therapy of diseases. The catalyst can be encapsulated into amphiphilic polymeric nanoparticles to generate artificial “nanozymes”. Similar to natural enzymes, the interactions of the host scaffold and the catalytic active centers modulate the catalytic performance of the resulting polymeric nanozymes, highlighting the biomimetic character of bioorthogonal nanozymes. We have designed a family of polymer-based bioorthogonal nanozymes by encapsulating Pd-based transition metal catalysts with varying ligand structures into a polymeric scaffold. By applying Michaelis-Menten analysis and comparing the behavior of each catalyst in its unencapsulated and encapsulated form, we found that the encapsulation into a polymer scaffold differentially modulates the activity of each catalyst, with widely varying nanozyme vs unencapsulated catalyst activities. These findings highlight the symbiotic relationship between catalyst and scaffold and emphasize the importance of the catalyst-scaffold interactions for designing bioorthogonal nanozymes.