PLGA Hollow Microbubbles Loaded with Iron Oxide Nanoparticles and Doxorubicin for Dual-mode US/MR Imaging and Drug Delivery

Abstract

We report here the fabrication, characterization and use of PLGA hollow microbubbles (HMs) loaded with iron oxide (Fe3O4) nanoparticles (NPs) and anticancer drug doxorubicin (DOX) for dual-mode ultrasound (US)/magnetic resonance (MR) imaging and drug delivery applications. In this study, a double emulsion technique was employed to prepare PLGA HMs, where hydrophobic superparamagnetic Fe3O4 NPs were encapsulated in the shell of the HMs, while DOX molecules were incorporated within the interior of the PLGA HMs. The formed multifunctional PLGA HMs were characterized via different techniques. We show that the HMs having a size of 1.0 μm are stable and can be potentially used as dual-mode contrast agents for US imaging and MR imaging applications. Furthermore, the HMs encapsulated with DOX are able to release DOX in a sustained manner with a higher release rate under an acidic pH condition than under the physiological pH condition. Importantly, cell viability assay data reveal that the DOX-loaded HMs are able to effectively inhibit the growth of cancer cells with a therapeutic efficacy comparable to free DOX. The fabricated PLGA-Fe3O4-DOX HMs could potentially be used as a theranostic agent for dual-mode US/MR imaging and anticancer drug delivery. Keywords: Doxorubicin, drug delivery, hollow microbubbles, iron oxide nanoparticles, MR imaging, US imaging.