Abstract
An acid-labile dextran-bortezomib conjugate (Dex-BTZ), i.e., a macromolecularized proteasome inhibitor, is synthesized by a boron esterification reaction. The prodrug exhibits intracellular acidity-accelerated BTZ release, and up-regulated inhibition efficacies toward hypoxic tumor in vitro and in vivo through both NF-κB- and ERS-mediated apoptosis signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Boronic Acids / chemistry*
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Bortezomib / chemistry*
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Bortezomib / pharmacology*
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Cell Hypoxia / drug effects
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Cell Line, Tumor
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Dextrans / chemistry*
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Drug Carriers / chemistry*
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Drug Liberation
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Esterification
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Humans
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Hydrogen-Ion Concentration
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Mice
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Signal Transduction / drug effects
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Up-Regulation / drug effects*
Substances
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Antineoplastic Agents
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Boronic Acids
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Dextrans
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Drug Carriers
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Bortezomib