Degradable ZnS-Supported Bioorthogonal Nanozymes with Enhanced Catalytic Activity for Intracellular Activation of Therapeutics

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 (V max) 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.

Molecular insights of nanozymes from design to catalytic mechanism

“…The metal nanoparticles provide a solid support for the active sites, simulating the second function of the natural enzymes' scaffolds. Besides, recently, Rotello and co-workers [71] open up a new avenue where nanoparticle-based scaffolds can also actively participate in catalysis as a cofactor and accelerate the chemical transformation that cannot be accomplished by natural enzymes. This work reported a bioorthogonal nanozyme using ZnS nanoparticles as a biodegradable and biocompatible scaffold, the encapsulation of [Cp*Ru(cod)Cl] inside the nanozyme monolayer, and ligand-mediated acceleration of catalysis, resulting in the activation of a chemotherapeutic drug (Figure 5c).…”

Bioorthogonal nanozymes: an emerging strategy for disease therapy

“…64 Ru-based bioorthogonal catalysts can be used not only in the form of complexes for therapeutic applications, but also in combination with nano-scaffolds to construct bioorthogonal nanozymes with excellent biodegradability, as in the study of Vincent M. Rotello. 65 He developed a novel bioorthogonal nanozyme (ZnS_NZ) by incorporating Ru-based [Cp*Ru(cod)Cl] complexes into the monolayers of ZnS nanoparticles (ZnS NPs), which endowed the [Cp*Ru(cod)Cl] catalyst with better catalytic activity, biocompatibility, and biodegradability (Fig. 3b).…”

Navigating zinc-involved nanomedicine in oncotherapy

“…In a recent work, Zhang et al chose ZnS nanoparticles (15 nm) as a tooling platform to embed ruthenium (Ru) catalysts into self-assembled monolayers on the particle surface, hence efficiently simulating the performance of natural enzymes. 56 Significantly, the biodegradation of ZnS nanoparticles realized the purpose of enhancing Ru catalysis by supplying thiolate surface ligands that accelerated the deallylation cycle rate in the bioorthogonal procedure. In fact, the maximum reaction rate was strikingly increased by approximately 2.5 folds compared with the non-biodegradable nano Au analogue at similar levels.…”