Gadolinium-Loaded Polychelating Polymer-Containing Tumor-Targeted Liposomes

Abstract

Magnetic resonance (MR) is one of the most widely used imaging modalities in contemporary medicine to obtain images of pathological areas. Still, there is a big effort to facilitate the accumulation of contrast in the required zone and further increase a local spatial concentration of a contrast agent for better imaging. Certain particulate carriers able to carry multiple contrast moieties can be used for an efficient delivery of contrast agents to areas of interest and enhancing a signal from these areas. Among those carriers, liposomes draw special attention because of their easily controlled properties and good pharmacological characteristics. To enhance the signal intensity from a given reporter metal in liposomes, one may attempt to increase the net quantity of carrier-associated reporter metal by using polylysine (PLL)-based polychelating amphiphilic polymers (PAP). In addition to heavy load of reporter metal onto the pharmaceutical nanocarrier (liposome), the accumulation of the contrast nanoparticles in organs and tissues of interest (such as tumors) can be significantly enhanced by targeting such particles both “passively,” via the so-called enhanced permeability and retention (EPR) effect, or “actively,” using various target-specific ligands, such as monoclonal antibodies. Combining three different properties – heavy load with Gd via the liposome membrane-incorporated PAP and tumor specificity mediated by the liposome-attached mAb 2C5 – in a single nanoparticle of long-circulating (PEGylated) liposomes could provide a new contrast agent for highly specific and efficient tumor MRI.