Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Abstract

Prodrug activation, by exogenously administered enzymes, for cancer therapy is an approach to achieve better selectivity and less systemic toxicity than conventional chemotherapy. However, the short half-lives of the activating enzymes in the bloodstream has limited its success. Demonstrated here is that a tyrosinase-MOF nanoreactor activates the prodrug paracetamol in cancer cells in a long-lasting manner. By generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of the enzymatic conversion of paracetamol is toxic to drug-resistant cancer cells. Tyrosinase-MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalized by cells, while free enzymes totally lose activity in a few hours. Thus, enzyme-MOF nanocomposites are envisioned to be novel persistent platforms for various biomedical applications.

Metal–Organic Frameworks for Biomedical Applications

“…e) Two types of mesoporous cavities in NPCN‐333(Al) and the size of TYR. Reproduced with permission 23. Copyright 2018, Wiley‐VCH.…”

“…In 2018, Zhou and co‐workers reported a highly efficient tyrosinase (TYR)‐MOF nanoreactor, that is, TYR@NPCN‐333(Al), for cancer treatment by activating a nontoxic prodrug paracetamol in tumor cells in a long‐lasting manner 23. NPCN‐333(Al), possessing three types of pores with diameters of 1.5, 4.2, and 5.5 nm, respectively, was synthesized from trimeric‐oxo clusters and a planar triangular ligands, 4,4′,4″‐ s ‐triazine‐2,4,6‐triyl‐tribenzoic acid (TATB), in N , N ‐dimethylformamide (DMF) under solvothermal condition, and was selected as the carrier for efficient encapsulation of TYR (Figure 2d,e).…”

When Nanozymes Meet Single‐Atom Catalysis

“…Enzymes are highly efficient biocatalysts that can selectively and specifically catalyze various reactions under mild conditions,a nd they have been used widely in disease diagnosis and cancer treatment. [1,2] However,t heir intrinsic limitations,s uch as high cost, low stability,a nd difficulties in recovery and storage,h ave inspired the exploration and development of enzyme mimics.Nanomaterials with enzymelike characteristics were recently discovered, which were defined as nanozymes by Weia nd Wang in 2013. [3] Fe 3 O 4 nanoparticles (NPs) with intrinsic peroxidase-like activity were proposed in 2007,; [4] subsequently more than ad ozen nanomaterials with enzyme-like characteristics were reported covering transition metals,n oble metals,a nd carbon nanomaterials.…”

Activation of Prodrugs by NIR‐Triggered Release of Exogenous Enzymes for Locoregional Chemo‐photothermal Therapy

“…To expand the range of prodrugs, a variety of functionalized exogenous enzymes have been applied to convert prodrugs for directed enzyme prodrug therapy . Meanwhile, metal–organic frameworks, polymers, and other carriers have been developed to solve the problems of high instability and rapid degradation of the exogenous enzymes in vivo. Although they have enormous potential, these strategies are still restricted owing to the whole‐body exposure and uncontrolled release of the enzymes.…”