Fouzi Mouffouk
Kuwait University, Kuwait
Title: Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging
Biography
Biography: Fouzi Mouffouk
Abstract
Early cancer detection is a major factor in the reduction of mortality and cancer management cost, the development of new tools for this purpose is of great value. Since healthy and pathological tissues as well as distinct diseases show similar magnetic moments, they produce a poor image contrast. In order to get a better anatomical differentiation and improve sensitivity, contrast agents (CAs) are used. Here, we present the development of a smart and targeted polymeric nanoparticle-based contrast agent (CA) for magnetic resonance imaging, able to turn on its imaging capability in the presence of target cancer cells. The new CA consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (PEG-b-PTMSMA), loaded with a gadolinium (III) complex (tBuBipyGd) and explores the acidic pH in cancer tissues. In vitro and in vivo experiments have shown that the designed nanoparticles are indeed pH-sensitive, in that they remained intact in neutral pH and turned on its imaging ability upon disruption in an acidic microenvironment. This encapsulation procedure significantly reduced the tBuBipyGd complex cytotoxicity towards Jurkat and MCF-7 cell lines. The targeting ability of nanoparticles towards cancer cells was enhanced by conjugation with the C595 monoclonal antibody against the human MUC1 protein, which is often overexpressed in breast cancer. Indeed, nanoparticle uptake by MUC1-expressing cells was higher for targeted than for non-targeted micelles. In addition, the uptake of targeted micelles by MUC1-expressing cells was stronger than by MUC1-negative cells.