Release of a Paramagnetic Magnetic Resonance Imaging Agent from Liposomes Triggered by Low Intensity Non-Focused Ultrasound

Abstract

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.

Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-Resolution 3-D Contrast-Enhanced Ultrasound Images: Role of Liposomes and Microbubbles

“…The mean hydrodynamic liposomes diameter was 160 ± 10 nm (determined by dynamic light scattering) and the final concentration of Gadoteridol in the liposomes suspension was 30 mM. We used liposomes with an internal core of an MRI contrast agent because in another related study we showed that these liposomes were visible by ultrasound imaging and that their release could be controlled by non-focused ultrasounds ( 22 ).…”

“…Liposomes, which are nano-sized vesicles, are widely used in medicine as drug carriers, mostly in cancer therapy ( 22 , 23 ). Recently, researchers have been facing the challenge of developing innovative strategies to provide an imaging support to therapies, including the design of probes for the in vivo visualization of drug delivery and release ( 24 , 25 ).…”

Sonosensitive MRI Nanosystems as Cancer Theranostics: A Recent Update

“…While the amount of cholesterol, saturated phospholipids, and polymers should be limited as they increase membrane stiffness and decrease the tendency to drug leakage, stealth moieties, like DSPE-PEG2000 seems to enhance sonosensitivity by the so called “antenna effect,” favoring the interactions between acoustic waves and the vesicles. Finally, Giustetto et al demonstrated that also shape, size, and intravesicular composition of liposomes may influence US triggered drug release (Giustetto et al, 2013 ).…”

Triggering Mechanisms of Thermosensitive Nanoparticles Under Hyperthermia Condition

“…Superparamagnetic iron oxide nanoparticles are a class of negative T 2 ‐contrast agents that can be incorporated in the liposomal formulations in order to enhance their intracellular delivery for magnetic resonance imaging (MRI) purposes . Appropriate selection of the phospholipid bilayer could result in a significant intracellular uptake of iron oxide nanoparticles with no cytotoxic effects .…”