Noninvasive Monitoring of Ultrasound-Induced CuO Nanoparticles Release from PEG-b-PLA Micelles using MRI

Background: Modern cancer therapeutic approaches combine different mechanisms in order to obtain a synergetic effect. Among these, the use of thermal therapy combined with administration of nanoparticles has gained popularity. During such procedures, the tumor is heated, either to ablative temperatures or to a level of thermal sensitization, yielding localized damage. Administration of nanoparticles, on the other hand, may offer a contrast enhancing effect for imaging, and/or produce better localization of temperature elevation, as well as serving as a therapeutic drug. This research explores the combined use of ultrasonic induced hyperthermia and controlled release of copper oxide nanoparticles (CuO NPs). These nanoparticles are visible by MRI and have also a therapeutic effect. The goal of this specific part, is to develop an image-guided noninvasive approach for monitoring ultrasonic induced controlled release of CuO NPs.

Methods: CuO NPs were first loaded into PEG-b-PLA micelles. Then, using a therapeutic ultrasonic transducer, samples of solutions containing the micelles loaded with the NPs were sonicated and their temperature was elevated to about 60^oC. The NPs release was quantified both by colorimetric methods and MR imaging.

Results: In addition to the observed temperature elevation, the ultrasound triggered the release of CuO NPs from the PEG-b-PLA micelles. This process was verified by comparison to non-treated samples. The controlled release process was detectable by T1 weighted MR imaging.

Conclusion: The combination of ultrasonic hyperthermia and micelle-encapsulated CuO NPs, released on demand and can be imaged by MRI, offers a new theranostic tool.