Development of targeted diagnostic and therapeutic tools for detection and treatment of oligodendrogliomas

Abstract

Carbonic anhydrase (CA) IX is an isoform of zinc metalloenzyme CA. It catalyzes the interconversion of carbon dioxide into proton and bicarbonate. CA IX is overexpressed in hypoxic environment due to rapidly proliferating cells. Therefore, it may be considered as a potent biomarker for the detection of various cancers including the brain. In this work, we have synthesized a small molecule ligand attached to a Rhodamine B conjugate as the detection tool. It will also be attached to super paramagnetic iron oxide nanoparticles (SPIONs) for the treatment of oligodendrogliomas using the principle of hyperthermia. The synthesized bioconjugate consists of three components: a) a small molecule inhibitor specific to the protein of interest (CA IX) b) a peptidic spacer to enhance the distance between targeting ligand and the fluorophore so as to not compromise on the specific binding affinity of the sulfonamide derivative as well as increase the hydrophilicity of the conjugate and c) a fluorophore (Rhodamine B) and a radioisotope chelator for the detection.