Synthesis of ligand targeted MRI contrast agent and nanoparticles as theranostic tool for hypoxic solid tumors

Abstract

Carbonic anhydrase (CA) is a Zinc metalloenzyme which catalyzes the interconversion of carbon dioxide into proton and bicarbonate. Most of the human cancers overexpresses CA IX which helps to control the hypoxic microenvironment in the cells. In this work, we have synthesized a ligand targeted MRI contrast agent for diagnosis of aggressive tumor progression and a ligand targeted therapeutic tool to deliver iron oxide nanoparticles. Iron oxide nanoparticles are being actively investigated to achieve highly efficient carcinogenic cell destruction through magnetic hyperthermia treatments. The designed molecule consists of three components: a) a small molecule inhibitor specific to the protein of interest e.g. aromatic sulphonamide derivative b) a peptidic spacer to enhance the distance between targeting ligand and the attached nanoparticle so, that the specific binding affinity of the ligand to the protein is not compromised and c) functionalized deliverable nanoparticle (Fe3O4) for MRI contrast agent as well as for magnetic hyperthermia treatment.