Inhibitor–Polymer Conjugates as a Versatile Tool for Detection and Visualization of Cancer-Associated Carbonic Anhydrase Isoforms

Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze hydration of carbon dioxide to bicarbonate. They play a crucial role in a number of important physiological processes. CAIX is a tumor-associated transmembrane isoenzyme that is overexpressed on the cell surface in hypoxic solid tumors and represents a validated target for cancer therapy and diagnosis. Here, we describe development of an N-(2-hydroxypropyl)­methacrylamide-based copolymer conjugate (iBody) containing a CAIX inhibitor for selective targeting of this enzyme on tumor cells. The iBody binds CAIX with sufficient affinity for use in biochemical applications. We show that the iBody can be used to isolate CAIX from cell lysates and to visualize it by flow cytometry and confocal microscopy. Our results demonstrate that the iBody is a valuable tool for targeting CAIX in vitro and with further development may serve as a platform for CAIX targeting in vivo.