Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound

Abstract

In the continuous search for cancer therapies with a higher therapeutic window, localized temperature-induced drug delivery may offer a minimal invasive treatment option. Here, a chemotherapeutic drug is encapsulated into a temperature-sensitive liposome (TSL) that is released at elevated temperatures, for example, when passing through a locally heated tumor. Consequently, high drug levels in the tumor tissue can be achieved, while reducing drug exposure to healthy tissue. Although the concept of temperature-triggered drug delivery was suggested more than thirty years ago, several chemical and technological challenges had to be addressed to advance this approach towards clinical translation. In particular, non-invasive focal heating of tissue in a controlled fashion remained a challenge. For the latter, high intensity focused ultrasound (HIFU) allows non-invasive heating to establish hyperthermia (40-45 °C) of tumor tissue over time. Magnetic resonance imaging (MRI) plays a pivotal role in this procedure thanks to its superb spatial resolution for soft tissue as well as the possibility to acquire 3D temperature information. Consequently, MRI systems emerged with an HIFU ultrasound transducer embedded in the patient bed (MR-HIFU), where the MRI is utilized for treatment planning, and to provide spatial and temperature feedback to the HIFU. For tumor treatment, the lesion is heated to 42 °C using HIFU. At this temperature, the drug-loaded TSLs release their payload in a quantitative fashion. The concept of temperature-triggered drug delivery has been extended to MR image-guided drug delivery by the co-encapsulation of a paramagnetic MRI contrast agent in the lumen of TSLs. This review will give an overview of recent developments in temperature-induced drug delivery using HIFU under MRI guidance.