Release of a paramagnetic magnetic resonance imaging agent from liposomes triggered by low Intensity non-focused ultrasound

Pulsed Low Intensity Non-Focused Ultrasound (LINFU) was used to trigger the release from liposomes of the clinically approved Magnetic Resonance Imaging (MRI) agent Gadoteridol. The extent of the release was monitored by relaxometric measurements upon changing both ultrasound stimulus (power, application times and mode, duty cycle values) and physico-chemical variables of the theranostic agent (liposomes size, shape, chemical composition, and concentration of the encapsulated agent). The release was not heat-mediated, but promoted by mechanical interactions between the acoustic radiation waves and the soft nanovesicles. The application of pulsed LINFU led to a controlled release detectable by both Nuclear Magnetic Resonance (NMR) relaxometry and MRI. Such promising observations were followed by an in vivo proof-of-concept study on a syngeneic B16 melanoma mouse model. The obtained results demonstrated the great potential of LINFU for designing MRI-guided protocols aimed at visualizing the release of drugs from liposomal carriers. This study could bring to the development of a new therapeutic for personalized medicine.