Diamagnetic chemical exchange saturation transfer (diaCEST) liposomes: Physicochemical properties and imaging applications

Chemical exchange saturation transfer (CEST) is a new type of magnetic resonance imaging (MRI) contrast based on labile spins which rapidly exchange with solvent, resulting in an amplification of signal which allows detection of solute protons at millimolar to micromolar concentrations. An additional feature of these agents is that natural organic and biodegradable compounds can provide strong CEST contrast, allowing the development of diamagnetic CEST (diaCEST) MRI contrast agents. The sensitivity of the CEST approach per unit of agent increases further when diaCEST contrast agents are loaded into liposomes to become diaCEST liposomes. In this review, we will discuss the unique and favorable features of diaCEST liposomes which are well suited for in vivo imaging. diaCEST liposomes are nanocarriers which feature high concentrations of encapsulated contrast material, controlled release of payload, and an adjustable coating for passive or active tumor targeting. These liposomes have water permeable bilayers and both the interior and exterior can be fine-tuned for many biomedical applications. Furthermore, a number of liposome formulations are used in the clinic including Doxil™, which is an approved product for treating patients with cancer for decades, rapid translation of these materials can be envisaged. diaCEST liposomes have shown promise in imaging of cancer, and monitoring of chemotherapy and cell transplants. The unique features of diaCEST liposomes are discussed to provide an overview of the applications currently envisioned for this new technology and to provide an overall insight of their potential.