Polymeric Vesicles Loaded with Gadoteridol as Reversible and Concentration-Independent Magnetic Resonance Imaging Thermometers

The use of temperature sensitive liposomes (TSLs) loaded with paramagnetic Gd(III) complexes have been explored to develop MRI agents able to provide a imaging guide to heating-based therapies. Though the performance of such probes has been already demonstrated in vivo at preclinical level, further improvements (e.g., concentration independent image response, reversibility of the sensor) are necessary to increase the accuracy of the temperature readout. This work reports for the first time, the potential of Gd-loaded polymersomes (bilayered vesicles made of amphiphilic di-block copolymers) as improved thermosensitive MRI probes. Differently from conventional TSLs, such probes do not display a defined gel-to-liquid temperature transition and, therefore, they did not release their content in a wide temperature range, thereby allowing reversible temperature readouts. Moreover, a ratiometric approach based on the measurement of the ratio between transverse and longitudinal water protons relaxation rates (R2/R1) allows a temperature readout independent of the probe concentration. The imaging performance of temperature sensitive polymersomes prepared in this work was tested both in vitro and in vivo after subcutaneous injection in healthy mice.