Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-05, Vol.57 (20), p.5725-5730
Main Authors: Lian, Xizhen, Huang, Yanyan, Zhu, Yuanyuan, Fang, Yu, Zhao, Rui, Joseph, Elizabeth, Li, Jialuo, Pellois, Jean‐Philippe, Zhou, Hong‐Cai
Format: Article
Language:English
Subjects:
Analgesics
Biocompatibility
Biomedical materials
Cancer
Cancer therapies
Cell death
Chemotherapy
drug delivery
Enzymes
Glutathione
metal–organic frameworks
Nanocomposites
nanoparticles
Paracetamol
Reactive oxygen species
Toxicity
Tyrosinase
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Summary: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. Covert delivery: Demonstrated here is activation of the prodrug paracetamol, by a tyrosinase‐MOF nanoreactor, in cancer cells in a long‐lasting manner. By generating reactive oxygen species and depleting glutathione, 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 lose activity in a few hours. MOF=metal–organic framework.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201801378