Superparamagnetic Oxygen-Loaded Nanobubbles to Enhance Tumor Oxygenation During Hyperthermia

Abstract

Tumor oxygenation is a critical issue for enhancing radiotherapy (RT) effectiveness. Alternating RT with hyperthermia improves tumor radiosensitivity by inducing a massive vasodilation of the neoangiogenic vasculature provided the whole tumor is properly heated. The aim of this work was to develop superparamagnetic oxygen-loaded nanobubbles (MOLNBs) as innovative theranostic hyperthermic agents to potentiate tumor oxygenation by direct intracellular oxygen administration. Magnetic oxygen-loaded nanobubbles were obtained by functionalizing dextran-shelled and perfluoropentane-cored nanobubbles with superparamagnetic iron oxide nanoparticles. Magnetic oxygen-loaded nanobubbles with sizes of about 380 nm were manufactured, and they were able to store oxygen and <i>in vitro</i> release it with prolonged kinetics. <i>In vitro</i> investigation showed that MOLNBs can increase tissue temperature when exposed to radiofrequency magnetic fields. Moreover, they are easily internalized by tumor cells, herein releasing oxygen with a sustained kinetics. In conclusion, MOLNBs can be considered a multimodal theranostic platform since, beyond their nature of contrast agent for magnetic resonance imaging due to magnetic characteristics, they showed echogenic properties and can be visualized using medical ultrasound.