Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 20, Pages 5725-5730Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201801378
Keywords
cancer; drug delivery; enzymes; metal-organic frameworks; nanoparticles
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Funding
- Welch Foundation through a Robert A. Welch Chair in Chemistry [A-0030]
- National Institutes of Health [R01GM110137]
- Strategic Transformative Research Program, College of Science, Texas AM University
- China Scholarship Council
- Youth Innovation Promotion Association CAS
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM110137] Funding Source: NIH RePORTER
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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.
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