Abstract
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting, and site-specific drug release are achieved, and as such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cathepsin B / metabolism*
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemistry
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Deoxycytidine / metabolism
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Deoxycytidine / pharmacokinetics
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Deoxycytidine / therapeutic use
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Drug Delivery Systems*
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Gemcitabine
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Male
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Mice
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Prodrugs / chemistry
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Prodrugs / metabolism
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Prodrugs / pharmacokinetics*
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Prodrugs / therapeutic use
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Rats, Sprague-Dawley
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Serum Albumin / metabolism*
Substances
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Prodrugs
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Serum Albumin
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Deoxycytidine
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Cathepsin B
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Gemcitabine