Nanoparticle-based chemical exchange saturation transfer (CEST) agents

The frequency-encoding property of chemical exchange saturation transfer (CEST) agents places them in a unique position among the MRI contrast agents, as it allows the visualization of more agents in the same MR image, as well as making it possible to set up innovative MRI-responsive agents. The sensitivity issue shown by molecular CEST agents (either diamagnetic or paramagnetic) has been tackled with the design of nanoparticle-based CEST agents endowed with a large number of exchangeable protons that ensure large saturation transfer levels. Several systems have been considered, namely supramolecular adducts, dendrimers, micelles and liposomes loaded with CEST agents (in most cases, paramagnetic CEST agents). A particularly sensitive system is represented by lipoCEST agents, consisting of liposomes whose inner water resonance is shifted by the co-presence of paramagnetic lanthanide complexes. The exchangeable pool of protons is represented by all the water molecules contained in the inner liposome cavity (106-108). Although in vitro work has provided excellent results, in vivo translation appears to be hampered to some extent by the peculiar behavior shown by these particles on administration to living animals.