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Evaluation of Nonpeptidic Ligand Conjugates for the Treatment of Hypoxic and Carbonic Anhydrase IX-Expressing Cancers.

Mol. Cancer Ther.. 2017; 
LvPeng-Cheng,RoyJyoti,PuttKarson S,LowPhil
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摘要

The majority of tumors contain regions of hypoxia, which cause marked phenotypic changes to resident cells. This altered gene expression often leads to increased resistance to anticancer treatments. Therefore, elimination of these resistant hypoxic cells is crucial to prevent disease recurrence. Herein, we describe the selective delivery of imaging and chemotherapeutic agents to cells expressing carbonic anhydrase IX (CA IX), a highly upregulated hypoxia receptor. These agents were conjugated to a potent divalent CA IX ligand through a hydrophilic PEG linker. These conjugates are shown to bind CA IX-expressing cells in a receptor-dependent manner with mid-nanomolar affinities and with good tumor selec... More

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