MRI monitoring of nanocarrier accumulation and release using Gadolinium-SPIO co-labelled thermosensitive liposomes

Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents triggered by hyperthermia, which can be, for example, precisely delivered using an MR Imaging-guided focused ultrasound procedure. In such a scenario, it is attractive to demonstrate the accumulation of liposomes before applying hyperthermia, as well as to document the release of liposome content using MRI. To address this need, thermosensitive liposomes were developed and characterized, which were doubly loaded by iron oxide nanoparticles and Gd-chelate, as opposed to loading with a single contrast agent. When intact, the transverse relaxivity of the liposomes is high allowing detection of carriers in tissue. After heating the longitudinal relaxivity steeply increases indicating release of the small molecular contents. By choosing the appropriate MR sequences, availability and release can be evaluated without interference of one contrast agent with the other.