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

Roana Noemi Schiopu Aresteanu 1 Alexander Borodetsky 2 Haim Azhari 1 Iris S. Weitz 2
1Technion-Israel Institute of Technology, Israel
2ORT Braude College, Israel

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 60oC. 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.

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