Abstract
Inhibitor–Polymer Conjugates as a Versatile Tool for Detection and Visualization of Cancer-Associated Carbonic Anhydrase Isoforms
Highlights
Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze reversible hydration of carbon dioxide to bicarbonate and protons.[1]
This tissue expression pattern suggests that CA IX (CAIX) might serve as a good target for diagnosis, imaging, and specific drug delivery to CAIX-expressing tumors.[5,12−15] CAIX positivity means a poor prognosis in lung, breast, cervical, brain and renal cancer, and neck cancer.[16−21] CAIX positive tumors are poorly responsive to conventional anticancer therapy, the disease relapses repeatedly, and tumors usually metastasize.[22−24]
The hydrophilic N-(2hydroxypropyl)methacrylamide (HPMA) copolymers are multivalent synthetic biocompatible macromolecules that carry a number of reactive groups enabling covalent attachment of various ligands such as fluorescent probes, therapeutics, peptides, oligonucleotides, and other low molecular weight compounds
Summary
Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze reversible hydration of carbon dioxide to bicarbonate and protons.[1] The 16 different CA isoforms identified in humans are involved in various physiological processes, including gluconeogenesis, lipogenesis, and ureagenesis.[2,3]. Some isoforms play important roles in the pathogenesis of diseases such as glaucoma, epilepsy, obesity, and cancer.[4,5]. The extracellular, membrane-bound CA IX (CAIX) isoform is overexpressed in cancer cells.[6] This isoenzyme is involved in regulating pH in hypoxic tumor cells and contributes to intercellular adhesion through its proteoglycan (PG) domain.[7]. This tissue expression pattern suggests that CAIX might serve as a good target for diagnosis, imaging, and specific drug delivery to CAIX-expressing tumors.[5,12−15] CAIX positivity means a poor prognosis in lung, breast, cervical, brain and renal cancer, and neck cancer.[16−21] CAIX positive tumors are poorly responsive to conventional anticancer therapy, the disease relapses repeatedly, and tumors usually metastasize.[22−24]
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