Enzymes and Prodrugs Used for ADEPT

Knox, Richard J.

doi:10.1007/978-1-4615-4823-2_4

Enzyme-Prodrug Strategies for Cancer Therapy 1999

DOI: 10.1007/978-1-4615-4823-2_4

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Enzymes and Prodrugs Used for ADEPT

Richard J. Knox

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2018

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Cited by 2 publications

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“…Tumor-specific accumulation of the enzyme activator is achieved by conjugation to tumor-directing antibodies or immunoliposomes. 15-17 While potentially useful, the biggest drawback is that externally administered enzymes are highly vulnerable to degradation in the bloodstream. 18 , 19 Thus the feasibility of this strategy remains unclear and strategies that can improve the biocompatibility of externally administered enzymes are needed.…”

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confidence: 99%

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

et al. 2018

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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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Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

et al. 2018

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Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Lian¹,

Zhu²,

Fang³

et al. 2018

Angewandte Chemie

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Prodrug activation, by exogenously administered enzymes,f or cancer therapyi sa na pproach 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 at yrosinase-MOF nanoreactor activates the prodrug paracetamol in cancer cells in al ong-lasting manner.B y generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of the enzymatic conversion of paracetamol is toxic to drug-resistant cancer cells.T yrosinase-MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalizedbycells,while free enzymes totally lose activity in af ew hours.T hus,e nzyme-MOF nanocomposites are envisioned to be novel persistent platforms for various biomedical applications.

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Enzymes and Prodrugs Used for ADEPT

Cited by 2 publications

References 75 publications

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

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